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Inventi Impact - Pharmacokinetics & Pharmacodynamics

Patent Watch

  • Methods for the formulation and manufacture of artesunic acid for injection

    A method for the manufacture of a sterile intravenous or intramuscular formulation of artesunic acid and the formulation are the subject of this invention. First the artesunic acid powder is sterilized with ethylene oxide and placed into a sterile container. The contained sterilized powder is then dissolved in sterile sodium phosphate buffered solution to produce an injectable intravenous or intramuscular formulation. The sodium phosphate dissolves and dilutes the artesunic acid powder without caking or frothing resulting in an improved drug product. The invention also relates to the formulation and a method of treating a patient with either uncomplicated or severe and complicated malaria.

  • IL-7 fusion proteins

    The invention is directed to a fusion protein which includes a first portion including an immunoglobulin (Ig) chain and a second portion including interleukin-7 (IL-7).

  • Enantiomerically pure phosphoindoles as HIV inhibitors

    3-phosphoindole compounds substantially in the form of a single enantiomer useful for the treatment of Flaviviridae virus infections, and particularly for HIV infections are provided. Also provided are pharmaceutical compositions comprising the 3-phosphoindole compounds alone or in combination with one or more other anti-viral agents, processes for their preparation, and methods of manufacturing a medicament incorporating these compounds.

  • N-terminally modified GLP-1 receptor modulators

    The subject matter described herein provides novel human glucagon-like peptide-1 (GLP-1) receptor modulators that have biological activity similar or superior to native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. The described compounds include chemically modified peptides that may stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 receptor modulators exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration. The disclosed and claimed peptides show desirable pharmacokinetic properties and desirable potency in efficacy models of diabetes.

  • Superior control of blood glucose in diabetes treatment

    Methods related to the treatment of diabetes and improving the control of blood glucose levels are provided. In particular, methods are provided for effectively reducing postprandial glucose excursions while reducing the incidence of clinically significant late postprandial hypoglycemia by administered an insulin composition in a form suitable for pulmonary administration. Additionally, methods for effectively reducing post-prandial glucose excursions while reducing the incidence of clinically significant late postprandial hypoglycemia by administered an insulin composition in a form suitable for pulmonary administration along with a long-acting basal insulin.

  • Simultaneous assay of target and target-drug binding

    Whole cell, simultaneous target and drug-target assay using differentially labeled antibodies and flow cytometry. First antibody binds to total target and second antibody binds to the drug binding site of the target, thus drug binding will competitively inhibit the second antibody allowing for a competitive inhibition assay of drug-target binding. The assay allows for whole cell analysis and even analysis of mixed populations of cells, yet provides detailed kinetic assessment of drug activity.

  • Modulators of pharmacokinetic properties of therapeutics

    The present application provides for a compound of Formula I, ##STR00001## or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.

  • FORMULATIONS OF LOW DOSE DICLOFENAC AND BETA-CYCLODEXTRIN

    The present invention is directed to a pharmaceutical composition containing a unit dose of a diclofenac compound effective to induce analgesia; and a beta-cyclodextrin compound; wherein the dose of the diclofenac compound is less than 10 mg. The present invention is also directed to methods of treating a subject in need of analgesia with the pharmaceutical compositions of the invention.

  • METHODS AND COMPOSITIONS FOR MODULATING DRUG-POLYMER ARCHITECTURE, PHARMACOKINETICS AND BIODISTRIBUTION

    Drug-polymer chemotherapeutics are provided having improved therapeutic efficacy and reduced dose-limiting toxicity. Methods are also provided for modulating the architecture, pharmacokinetics and biodistribution of drug-polymers and for reducing the dependence of transition temperature on concentration for drug-polymers.

  • CLOSED-LOOP GLUCOSE CONTROL STARTUP

    Disclosed are methods, systems, etc. for closed-loop glucose control startup. In certain example embodiments, a request for entry of an automatic mode of operation of a glucose monitoring and insulin delivery system for a patient may be detected. An entry of the automatic mode of operation may be controlled based, at least in part, on a detected rate of change of blood glucose concentration of the patient. In certain other example embodiments, initiation of a continual phase of an automatic mode of operation may be controlled based, at least in part, on a time since a most recent manual delivery of a bolus, on a detected rate of change of blood glucose concentration, on a targeted fixed set point, a combination thereof, and so forth.

  • 12-HOUR SUSTAINED-RELEASE METOCLOPRAMIDE

    The present invention consists of an extended-release metoclopramide hydrochloride pharmaceutical composition, in 15 mg drug substance tablets, for use in gastrointestinal disorders. The formulation is mainly composed of a hydrophilic polymer, a hydrophobic polymer, a hydrophilic component and metoclopramide hydrochloride. The hydrophilic polymer is swollen by hydration when contacting water, forming a gel coat which controls drug substance release. The water inside the matrix dissolves the drug substance and this is diffused outside through the gel coat. The hydrophobic polymer shows plastic deformation properties under compression, tending to surround the drug substance particles reducing the pore quantity and dimensions in the matrix structure, delaying as a consequence the drug substance release. The hydrophilic component is part of the gel coating structure providing support thereto. Drug substance is the metoclopramide hydrochloride or a pharmaceutically acceptable salt thereof.

  • Oral Formulations of Chemotherapeutic Agents

    The present invention is directed to new oral formulations of chemotherapeutic agents, their process of preparation as well as their therapeutic uses. More specifically, said invention is related to nanoparticles comprising at least one chemotherapeutic agents as an active ingredient, at least one polymer and at least one cyclic oligosaccharide capable of complexing said camptothecin derivative, said nanoparticles being for therapeutic oral administration.

  • FORMULATIONS FOR ENHANCED BIOAVAILABILITY OF ORALLY ADMINISTERED POLAR AGENTS

    A composition is described having improved oral permeability of polar agents such as neuraminidase inhibitors. The composition includes one or more polar agents and one or more permeability enhancers such that the composition increases the amount of the polar agent capable of being transported across a Caco-2 cell membrane by at least 150% relative to the amount capable of being transported across the Caco-2 Cell membrane in the absence of the permeability enhancer. Oral dosage forms including the composition, and methods of treating or preventing influenza infection are also provided.

  • METHOD AND APPARATUS FOR IDENTIFYING A SAFE AND EFFICACIOUS DOSING REGIMEN

    The invention features methods and systems to provide, in one test session, information on the patient's sensitivity to a probe drug for treating attentional disorders. The methods and systems of the invention can enable clinicians and consumers to ascertain how much benefit an individual would derive from treatment, what dose would be required, and the acute effect of that dose on regularity and rhythmicity of their heartbeat.

  • Process for PEGylation of Proteins

    The present invention relates to a process for improving pegylation reaction yield of r-metHuG-CSF comprising conjugating r-metHuG-CSF to a PEG aldehyde at a free amine moiety at the N terminal end on the G-CSF in presence of a reducing agent in a pegylation buffer solution comprising a polyol having the formula C.sub.nH.sub.2n+2O.sub.n where n is from 3 to 6, or a carbohydrate, or a derivative thereof wherein the concentration of said polyol or carbohydrate or derivative thereof is in the range of 0.1% to 10% w/w.

  • BIODEFENSES USING TRIAZOLE-CONTAINING MACROLIDES

    Use of macrolide and ketolide antibiotics for the treatment of acute exposure and diseases caused by biodefense pathogens is described.

  • INTERFERON ALPHA-INDUCED PHARMACODYNAMIC MARKERS

    The present invention encompasses type-I IFN and IFN.alpha.-induced PD marker expression profiles, kits, and methods for identifying such IFN.alpha.-induced PD marker expression profiles. The type-I IFN and IFN.alpha.-induced PD marker expression profiles may also be used in, for example, methods of treating patients having a type-I IFN or IFN.alpha.-mediated disorder, methods of monitoring disease progression of patients receiving treatment with a therapeutic agent that binds to and modulates IFN.alpha. activity, identifying patients as candidates to receive a therapeutic that binds to and neutralizes IFN.alpha. activity, and in diagnosing or providing a prognoses to patients having IFN.alpha.-induced disorders.

  • ORAL DOSAGE FORMS WITH THERAPEUTICALLY ACTIVE AGENTS IN CONTROLLED RELEASE CORES AND IMMEDIATE RELEASE GELATIN CAPSULE COATS

    The present invention relates to oral dosage form with active agents in controlled release cores and in immediate release gelatin capsule coats.

  • BINDING-SITE MODIFIED LECTINS AND USES THEREOF

    In one aspect, the disclosure provides cross-linked materials that include multivalent lectins with at least two binding sites for glucose, wherein the lectins include at least one covalently linked affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with glucose for binding with the lectins at said binding sites and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between lectins and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of glucose. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label.

  • CRYSTALLINE INSULIN-CONJUGATES

    The present disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.

  • PHARMACOKINETIC CONTROL FOR OPTIMIZED INTERFERON DELIVERY

    Methods and devices for treating patients having chronic hepatitis C infection so as to eradicate detectable HCV-RNA and/or inhibit the emergence of a drug resistant HCV variant are disclosed. Certain methods of the invention involve the use of a continuous infusion pump in a multiphasic combination therapy using a therapeutically effective amount of a small molecule inhibitor such as ribavirin and a therapeutically effective amount of interferon-.alpha.

  • METHOD FOR THE PREPARATION OF A HIGH-TEMPERATURE STABLE OXYGEN-CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION AND THE USE THEREOF

    A high temperature-stable and highly purified .alpha.-.alpha. cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells obtained from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents the lysis of white blood cells. Nucleic acids from white blood cells and the phospholipids impurities are not detected. The blocking of reactive sulfhydryl groups in hemoglobin by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography is used to remove different plasma protein impurities. N-acetyl cysteine is added to the .alpha.-.alpha. cross-linked tetrameric hemoglobin solution to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion. The product finds use in tissue oxygenation and cancer treatment.

  • Optimized Drug Conjugates

    The invention generally relates to optimized drug conjugates.

  • PHARMACEUTICAL COMPOSITIONS PROVIDING ENHANCED DRUG CONCENTRATIONS

    A drug in a solubility-improved form is combined with a concentration-enhancing polymer in a sufficient amount so that the combination provides substantially enhanced drug concentration in a use environment relative to a control comprising the same amount of the same solubility-improved form of drug without the concentration-enhancing polymer.

  • Granulate Formulation of Pirfenidone and Pharmaceutically Acceptable Excipients

    A capsule formulation of pirfenidone is provided that includes pharmaceutically acceptable excipients. In one embodiment, this capsule formulation is capable of sustaining desirable pharmacokinetic responses in a patient. Further provided are methods of treating fibrotic conditions and other cytokine-mediated disorders by administering pirfenidone capsules of such formulation to a patient in need.

  • DELAYED RELEASE RASAGILINE FORMULATION

    Disclosed are formulations of rasagiline base which are designed to delay release of rasagiline while maintaining specific pharmacokinetic properties. Also, disclosed are rasagiline citrate salt and the use and process of manufacture thereof.

  • COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS

    The invention provides compositions, kits and methods utilizing polypeptides having a viral alpha-helix heptad repeat domain in a stabilized a-helical structure (herein also referred to as SAH). The compositions are useful for treating and/or preventing viral infections. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled alpha helical peptides display excellent proteolytic, acid, and thermal stability, restore the native alpha-helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.

  • CONJUGATE BASED SYSTEMS FOR CONTROLLED DRUG DELIVERY

    Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

  • NOVEL DERIVATIVES OF 3,3-DIPHENYLPROPYLAMINES

    The invention concerns novel derivatives of 3,3-diphenylpropylamines, methods for their preparation, pharmaceutical compositions containing the novel compounds, and the use of the compounds for preparing drugs. More particularly, the invention relates to novel prodrugs of antimuscarinic agents with superior pharmacokinetic properties compared to existing drugs such as oxybutynin and tolterodine, methods for their preparation, pharmaceutical compositions containing them, a method of using said compounds and compositions for the treatment of urinary incontinence, gastrointestinal hyperactivity (irritable bowel syndrome) and other smooth muscle contractile conditions.

  • FVIII Muteins for Treatment of Von Willebrand Disease

    This invention relates to treatment of von Willebrand Disease by administration of Factor VIII muteins that are covalently bound, at a predefined site that is not an N-terminal amine, to one or more biocompatible polymers such as polyethylene glycol. The mutein conjugates retain FVIII procoagulant activity and have improved pharmacokinetic properties in subjects lacking von Willebrand Factor.

  • NOVEL TRIFLUOROMETHYLSULFONAMIDE GAMMA SECRETASE INHIBITOR

    The present invention is directed to a novel trifluoromethylsulfonamide derivative which inhibits the processing of APP by the putative .gamma.-secretase and thus is useful in the treatment or prevention of Alzheimer's disease. This compound possesses favorable pharmacokinetic properties in higher species (rhesus) and thus can be dosed on an intermittent dosing regiment (e.g., once weekly). When dosed on such a regiment the compound exhibits significant and continuous A.beta. lowering without the manifestation of Notch associated gastrointestinal toxicity for extended periods, e.g., 7 days. Pharmaceutical compositions and methods of use are also included.

  • Tacrolimus For Improved Treatment Of Transplant Patients

    An extended release oral dosage form comprising as active substance tacrolimus or a pharmaceutically active analogue thereof for a once daily immunosuppressive treatment of a patient in need thereof, preferable a kidney or liver transplant patient. The dosage form releases the active substance over an extended period of time. It also provides improved pharmacokinetic parameters due to an extended and constant in vivo release including substantial decreased peak concentrations, despite increased bioavailability, substantial extended times for maximal concentration, and higher minimal concentrations when compared with conventional immediate release dosage forms and a recent modified release tacrolimus dosage form.

  • DIALKYLAMINO ALKYL ESTERS OF PIVAGABINE AS MEDICAMENTS FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS

    The present embodiments are related to the compound of Formula 1 or Formula 2 below and pharmaceutical formulations thereof as well as treatments for a wide variety of Central Nervous System disorders with the pharmaceutical formulations. Some embodiments include the use of a variety of the instant compounds which surprisingly and advantageously exhibit improved pharmacokinetic and therapeutic profiles in comparison to pivagabine. ##STR00001##

  • CONJUGATES OF A POLYPEPTIDE AND AN OLIGOSACCHARIDE

    The present invention relates to conjugates of a polypeptide and an oligosaccharide, wherein the polypeptide is conjugated to at least one oligosaccharide-spacer residue, the oligosaccharide being a synthetic sulfated oligosaccharide comprising 4-18 monosaccharide units and per se having affinity to antithrombin III and the spacer being a bond or an essentially pharmacologically inactive flexible linking residue, or a pharmaceutically acceptable salt thereof. The conjugates of the invention have improved pharmacokinetic properties when compared to the original polypeptides (i.e. the corresponding non-conjugated polypeptides per se).

  • Tacrolimus For Improved Treatment Of Transplant Patients

    An extended release oral dosage form comprising as active substance tacrolimus or a pharmaceutically active analogue thereof for a once daily immunosuppressive treatment of a patient in need thereof, preferable a kidney or liver transplant patient. The dosage form releases the active substance over an extended period of time. It also provides improved pharmacokinetic parameters due to an extended and constant in vivo release including substantial decreased peak concentrations, despite increased bioavailability, substantial extended times for maximal concentration, and higher minimal concentrations when compared with conventional immediate release dosage forms and a recent modified release tacrolimus dosage form.

  • PHARMACOKINETICALLY-BASED DOSING REGIMENTS OF A THROMBIN RECEPTOR ANTAGONIST

    Dosing regimens based on the pharmacokinetic characteristics of a thrombin receptor antagonist are disclosed. In some embodiments, the dosing regimens result in mean plasma concentrations. Also disclosed are methods of treating acute coronary syndrome and peripheral arterial disease, and of effecting secondary prevention, by orally administering thrombin receptor antagonists according to such dosing regimens.

  • TESTOSTERONE GEL AND METHOD OF USE

    The present invention relates to an improved transdermal hydroalcoholic testosterone gel formulation that provides, among other things, a desirablepharmacokinetic hormone profile, and methods of use.

  • STABLE PHARMACEUTICAL COMPOSITION FOR ATHEROSCLEROSIS

    The present invention relates to a stable solid oral pharmaceutical multi-component composition comprising combination of blood pressure lowering drugs with lipid lowering agent/s and optionally a platelet aggregation inhibitor in a single dosage form. The blood pressure lowering agents are selected from .beta.-adrenergic receptor blocking agent, ACE inhibitor and diuretic. The lipid lowering agent is selected from HMG Co-enzyme-A reductase inhibitor. The pharmaceutical composition made as per present invention a) overcomes any drug-drug interactions, b) exhibits pharmacokinetic and pharmacodynamic profile of individual therapeutic agent, c) has minimal side effects. The invention provides multi-component composition (MCC) to increase adherences to therapy. The MCC as per present invention provides compositions that maintain activity of all active ingredients without significant increase in adverse event profile. The present invention further relates to a method of preparing the said pharmaceutical composition.

  • Pyrazine Derivatives for Optical Imaging and Therapy

    The invention provides compounds, including compositions, preparations and formulations, and methods of using and making such compounds. Compounds of the present invention include pyrazine derivatives having a pyrazine core and a plurality of substituents. In some embodiments, pyrazine derivatives of the invention are pyrazine core compounds having one or more electron donating groups and one or more electron withdrawing groups optionally functionalized to provide useful optical, biological, pharmacokinetic and/or physical properties.

  • Granulate Formulation of Pirfenidone and Pharmaceutically Acceptable Excipients

    A capsule formulation of pirfenidone is provided that includes pharmaceutically acceptable excipients. In one embodiment, this capsule formulation is capable of sustaining desirable pharmacokinetic responses in a patient. Further provided are methods of treating fibrotic conditions and other cytokine-mediated disorders by administering pirfenidone capsules of such formulation to a patient in need.

  • DELAYED RELEASE RASAGILINE FORMULATION

    Disclosed are formulations of rasagiline base which are designed to delay release of rasagiline while maintaining specific pharmacokinetic properties. Also, disclosed are rasagiline citrate salt and the use and process of manufacture thereof.

  • STABLE PHARMACEUTICAL COMPOSITION FOR ATHEROSCLEROSIS

    The present invention relates to a stable solid oral pharmaceutical multi-component composition comprising combination of blood pressure lowering drugs with lipid lowering agent/s and optionally a platelet aggregation inhibitor in a single dosage form. The blood pressure lowering agents are selected from .beta.-adrenergic receptor blocking agent, ACE inhibitor and diuretic. The lipid lowering agent is selected from HMG Co-enzyme-A reductase inhibitor. The pharmaceutical composition made as per present invention a) overcomes any drug-drug interactions, b) exhibits pharmacokinetic and pharmacodynamic profile of individual therapeutic agent, c) has minimal side effects. The invention provides multi-component composition (MCC) to increase adherences to therapy. The MCC as per present invention provides compositions that maintain activity of all active ingredients without significant increase in adverse event profile. The present invention further relates to a method of preparing the said pharmaceutical composition.

  • MICROFLUIDIC DEVICE FOR PHARMACOKINETIC-PHARMACODYNAMIC STUDY OF DRUGS AND USES THEREOF

    A microfluidic device for culturing cells, termed a microscale cell culture analog (.mu.CCA), is provided. The microfluidic device allows multiple cell or tissue types to be cultured in a physiologically relevant environment, facilitates high-throughput operation and can be used for drug discovery. The microfluidic device uses gravity-induced fluidic flow, eliminating the need for a pump and preventing formation of air bubbles. Reciprocating motion between a pair of connected reservoirs is used to effect the gravity-induced flow in microfluidic channels. Bacterial contamination is reduced and high throughput enabled by eliminating a pump. The microfluidic device integrates a pharmacokinetic-pharmacodynamic (PK-PD) model to enable PK-PD analyses on-chip. This combined in vitro/in silico system enables prediction of drug toxicity in a more realistic manner than conventional in vitro systems.

  • BISMUTH-CONTAINING COMPOUNDS, COORDINATION POLYMERS, METHODS FOR MODULATINGPHARMACOKINETIC PROPERTIES OF BIOLOGICALLY ACTIVE AGENTS, AND METHODS FOR TREATING PATIENTS

    Bismuth-containing compounds include bismuth and a biologically active agent coordinated to the bismuth. The biologically active agent includes at least one heteroatom configured for coordination with the bismuth. Coordination polymers include a polymer matrix that contains a bismuth-containing compound. Methods for modulating a pharmacokinetic property of a biologically active agent include coordinating the biologically active agent to bismuth to form a bismuth-containing compound, and administering the bismuth-containing compound orally to a patient. Methods for treating Parkinson's disease, methods for treating hypothyroidism, methods for treating ulcerative colitis, and methods for treating cancer each include administering a bismuth-containing compound to a patient.

  • POLYMER-DRUG CONJUGATES

    A conjugate that includes a drug covalently linked to a polymer. Upon administration, the conjugate is digested by an enzyme that is present at the site of administration thereby releasing a therapeutic agent. The conjugate may demonstrate substantially the same pharmacokinetic and pharmacodynamic behavior as the drug itself. A material for controllably releasing a conjugate in response to the local concentration of a molecular indicator. The material includes a plurality of conjugates and a plurality of multivalent cross-linking agents. The polymers of the conjugates include an analog of the indicator within their covalent structure. The multivalent cross-linking agents include cross-link receptors that interact with the indicator analog and thereby cross-link the conjugates. These non-covalent interactions are competitively disrupted when an amount of the molecular indicator is present thereby causing the material to release the conjugate in a manner that is dependent on the local concentration of indicator.

  • Systems And Methods For Measuring And Modeling In Vivo Manganese Ion Transport In A Subject

    Described herein are systems and methods for quantitatively measuring manganese ion efflux in a subject. In general, the systems and methods compare imaging data from a subject taken over specific periods of time to pharmacokinetic models in order to measure manganese ion efflux rates from an organ in a subject. By understanding the specific location and rate of manganese ion efflux and influx from the organ, it is possible to more accurately correlate calcium ion activity. Calcium ion efflux is associated with a number of biological mechanisms in the subject, and the methods and systems described herein can be used as a diagnostic tool not only for monitoring calcium efflux in the subject but also aid in the treatment of diseases associated with changes in calcium ion efflux.

  • DELAYED RELEASE RASAGILINE MALATE FORMULATION

    Disclosed are formulations which are designed to delay release of rasagiline while maintaining specific pharmacokinetic properties.

  • Bioavailability Enhancement Delivery System

    A composition for increasing the bioavailability of drugs in humans and animals comprising a microemulsion further comprising a first emulsifier, a second emulsifier, and an oil wherein the emulsifiers have individual HLB values of between about 10 and about 30, are in a ratio ranging from about 1:1 to about 4:1; and, the first and second emulsifier combination and oil are in a ratio of about 99:1 to about 9:1. A method for increasing the bioavailability of such a composition is also provided.

  • NOVEL TRIAZOLE DERIVATIVES WITH IMPROVED RECEPTOR ACTIVITY AND BIOAVAILABILITY PROPERTIES AS GHRELIN ANTAGONISTS OF GROWTH HORMONE SECRETAGOGUE RECEPTORS

    The present invention provides novel triazole derivatives with improved receptor activity and bioavailability properties as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular alcohol disorder, drug abuse, growth retardation, cachexia, short-, medium-, and/or long term regulation of energy balance, short-, medium-, and/or long term regulation (stimulation and/or inhibition) of food intake, intake of rewarding food, adipogenesis, adiposity and/or obesity, body weight gain and/or reduction, diabetes, diabetes type I, diabetes type II, tumor cell proliferation, inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy).

  • Enhanced Absorption of Omega Fatty Acid Oils

    A composition for increasing the bioavailability of oils in humans and animals comprising mixing a first emulsifier and a second emulsifier in a ratio ranging from about 1:1 to about 3:1 with a consumable oil wherein the first emulsifier is polyoxyethylene sorbitan monooleate and the second emulsifier is tocopheryl polyethylene glycol succinate. A method for increasing the bioavailability of such a composition is also provided.

  • METHOD OF INCREASING THE EXTENT OF ABSORPTION OF TIZANIDINE

    An article and method for increasing the extent of tizanidine absorption in a patient receiving tizanidine therapy. Tizanidine may be administered in the form of an immediate release tablet composition at or around the time food is consumed. The composition may be packaged in a container for distribution.

  • Method to Increase the Absorption of Unsaturated Fatty Acids by Human Infants

    The present invention relates to a method to increase the absorption by a human infant of at least one unsaturated fatty acid, said method comprising the enteral administration to said infant of recombinant human bile-salt-stimulated lipase (rhBSSL). In another aspect the invention also relates to a method to improve the visual and/or cognitive development of a human infant, said method comprising the enteral administration to said infant of rhBSSL. Such methods have particular utility for preterm human infants, particular those in medical need of increasing their absorption of or availability to such unsaturated fatty acids. In further aspects, the invention relates to kits, packaged-pharmaceutical-products, recombinant human bile-salt-stimulated lipase and pharmaceutical compositions, in each case useful for increasing the absorption by a human infant of at least one unsaturated fatty acid, or for increasing the visual and/or cognitive development of a human infant.

  • NOVEL COMPOUNDS THAT ARE USEFUL FOR IMPROVING PHARMACOKINETICS

    Novel compounds of formula 1 ##STR00001## or a pharmaceutically acceptable salt thereof inhibit cytochrome P450 monooxygenase.

  • Compositions And Methods For Modulating The Pharmacokinetics and Pharmacodynamics of Insulin

    Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of rapid acting injectable insulin formulations are described herein. In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid ("EDTA") and a dissolution/stabilization agent, and optionally additional excipients. Calcium disodium EDTA is less likely to remove calcium from the body, and typically has less pain on injection in the subcutaneous tissue. Modulating the type and quantity of EDTA can change the insulin absorption profile. Increasing the quantity of citrate can further enhance absorption and chemically stabilize the formulation. In the preferred embodiment, the formulation contains human insulin, calcium disodium EDTA and a dissolution/stabilization agent such as citric acid or sodium citrate. These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection.

  • HUMAN PROTEIN SCAFFOLD WITH CONTROLLED SERUM PHARMACOKINETICS

    This invention provides constructs comprising a protein scaffold, wherein the scaffold comprises Domain III, Domain IIIa, or Domain IIIb of human serum albumin or a polypeptide having substantial sequence identity to the Domain III, the Domain IIIa, or the Domain IIIb; and a targeting moiety in covalent linkage to the protein scaffold; and a therapeutic moiety and/or an imaging moiety in covalent linkage to the protein scaffold. The scaffold can be modified to tune the serum pharmacokinetics of the construct. In addition to methods of making the constructs, therapeutic, imaging and diagnostic uses of the constructs are also provided.

  • Compositions And Methods For Modulating The Pharmacokinetics and Pharmacodynamics of Insulin

    Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of rapid acting injectable insulin formulations are described herein. In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid ("EDTA") and a dissolution/stabilization agent, and optionally additional excipients. Calcium disodium EDTA is less likely to remove calcium from the body, and typically has less pain on injection in the subcutaneous tissue. Modulating the type and quantity of EDTA can change the insulin absorption profile. Increasing the quantity of citrate can further enhance absorption and chemically stabilize the formulation. In the preferred embodiment, the formulation contains human insulin, calcium disodium EDTA and a dissolution/stabilization agent such as citric acid or sodium citrate. These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection.

  • USE OF PRODRUGS TO AVOID GI MEDIATED ADVERSE EVENTS

    The present invention relates to prodrugs of a wide variety of drugs and pharmaceutical compositions containing such prodrugs. Methods for minimizing locally mediated (from within the gut lumen) adverse gastrointestinal events associated with the underivatised drug and increasing the sustainment of plasma drug levels with the aforementioned prodrugs are also provided. Thus, the present invention relates to the use of prodrugs of a wide diversity of drugs (other than opioids) to transiently inactivate them and so reduce directly, locally mediated adverse gastrointestinal (GI) side-effects normally evident after administration of the parent compound. Additionally, such prodrugs may confer improved pharmacokinetics.

  • COMPOSITIONS CONTAINING GLYCOSYLATED ANTIBODIES AND USES THEREOF

    The present invention provides compositions of antibodies, e.g., human antibodies, of varying glycosylation structures that serve to achieve desired rates of serum clearance. The invention also provides methods for modulating the pharmacokinetics of antibodies, e.g., human antibodies, and therapeutic compositions containing such antibodies. These methods rely on varying the glycosylation structures of the antibodies, e.g., human antibodies, to achieve desired rates of serum clearance.

  • GALANTAMINE AMINO ACID AND PEPTIDE PRODRUGS AND USES THEREOF

    Prodrugs of galantamine or its 3-hydroxy metabolite with amino acids or short peptides, pharmaceutical compositions containing such prodrugs and methods for treating a memory or cognition disorder with the galantamine prodrugs are provided herein. Prodrugs having side chains of valine, phenylalanine, tyrosine or para amino benzoic acid and mono-, di- and tripeptides thereof are preferred. Additionally, methods for avoiding or minimizing the adverse gastrointestinal side effects associated with galantamine administration, as well as improving the pharmacokinetics of galantamine are provided herein.

  • PRODRUGS OF GUANFACINE

    Prodrugs of guanfacine with amino acids or short peptides, pharmaceutical compositions containing such prodrugs and a method for providing therapeutic benefit in the treatment of ADHD/ODD (attention deficient hyperactivity disorder and oppositional defiance disorder) with guanfacine prodrugs are provided herein. Additionally, methods for minimizing or avoiding the adverse gastrointestinal side effects associated with guanfacine administration, as well as improving the pharmacokinetics of guanfacine are provided herein.

  • PHARMACOKINETICS OF IONTOPHORETIC SUMATRIPTAN ADMINISTRATION

    Improved pharmacokinetic profiles for the iontophoretic delivery of sumatriptan are described.

  • Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases

    The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated form of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

  • Compositions and Methods of Use of Immunotoxins Comprising Ranpirnase (Rap) Show Potent Cytotoxic Activity

    The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 or anti-CD22 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.

  • ANTIBODY MOLECULES THAT BIND TO IL-6 RECEPTOR

    The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.

  • COMPOUNDS WITH REDUCED RING SIZE FOR USE IN DIAGNOSING AND TREATING MELANOMA, INCLUDING METASTATIC MELANOMA AND METHODS RELATED TO SAME

    The present invention is directed to novel non-invasive diagnostic tools/compounds to image cancers, especially, melanoma, including metastatic melanoma in vivo. The present compounds exhibit enhanced uptake in cancerous cells and tissue and decreased renal uptake in kidney, evidencing favorable pharmacokinetics of compounds of the present invention. The compounds according to the present invention represent an advance in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention are also useful for initiating therapy for melanoma as well as monitor patients' response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma/metastatic melanoma. Compounds according to the present invention may be used as diagnostic tools for a number of conditions and diseases states as well as therapeutic agents for treating such conditions and disease states.

  • CONJUGATES WITH IMPROVED PHARMACOKINETIC PROPERTIES

    The present invention concerns methods and means for modulating pharmacokinetic properties of molecules, such as biologically active molecules. More specifically, the present invention concerns conjugates comprising a biologically active moiety and a moiety conjugated to and modulating at least one pharmacokinetic property of the biologically active moiety (pharmacokinetic property modulating moiety).

  • IMAGING AGENTS WITH IMPROVED PHARMACOKINETIC PROFILES

    The invention relates to compounds suitable for use in an imaging agent said imaging agent showing an improved pharmacokinetic profile.

  • MODULATORS OF PHARMACOKINETIC PROPERTIES OF THERAPEUTICS

    The present application provides for a compound of Formula IV, ##STR00001## or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.

  • Devices and Methods for Pharmacokinetic-Based Cell Culture System

    Devices, in vitro cell cultures, systems, and methods are provided for microscale cell culture analogous (CCA) device.

  • THIAZOLYL MGLUR5 ANTAGONISTS AND METHODS FOR THEIR USE

    The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

  • SUBCUTANEOUS PALIPERIDONE COMPOSITION

    The present invention relates to pharmaceutical composition for subcutaneous injection comprising a paliperidone compound wherein the composition releases the paliperidone with an immediate onset of action and continuously for at least 3 weeks, and wherein the composition has a pharmacokinetic profile in vivo with substantially no burst release of the paliperidone. The compositions are useful as medicaments for the treatment of psychotic disorders and diseases.

  • COMPOSITION FOR ADMINISTERING AN NMDA RECEPTOR ANTAGONIST TO A SUBJECT

    The invention provides compostions for administering memantine to a subject. Memantine in an extended release form containing 22.5 to 30 mg memantine or a pharmaceutically acceptable salt achieves particularpharmacokinetic criteria such as change in plasma concentration of memantine over time and ratio of maximum memantine plasma concentration to mean memantine plasma concentration.

  • METHOD FOR ADMINISTERING AN NMDA RECEPTOR ANTAGONIST TO A SUBJECT

    The invention provides compostions for administering memantine to a subject. Memantine in an extended release form containing 22.5 to 30 mg memantine or a pharmaceutically acceptable salt achieves particularpharmacokinetic criteria such as change in plasma concentration of memantine over time and ratio of maximum memantine plasma concentration to mean memantine plasma concentration.

  • METHODS FOR THE TREATMENT OF CNS-RELATED CONDITIONS

    The invention provides methods for administering extended release memantine in combination with immediate release donepezil to a subject. Memantine in an extended release form containing 22.5 to 30 mg memantine or a pharmaceutically acceptable salt thereof in combination with donepezil is administered to a patient suffering from a neurological condition, such as Alzheimer's disease, Parkinson's disease or dementia. The extended release form of memantine achieves particular pharmacokinetic criteria such as change in plasma concentration of memantine over time and ratio of maximum memantine plasma concentration to mean memantine plasma concentration.

  • COMPOSITIONS FOR THE TREATMENT OF CNS-RELATED CONDITIONS

    The invention provides compositions comprising extended release memantine in combination with immediate release donepezil to a subject. Memantine in an extended release form containing 22.5 to 30 mg memantine or a pharmaceutically acceptable salt thereof in combination with donepezil achieves particular pharmacokinetic criteria such as change in plasma concentration of memantine over time and ratio of maximum memantine plasma concentration to mean memantine plasma concentration.

  • DELAYED RELEASE RASAGILINE FORMULATION

    Disclosed are formulations which are designed to delay release of rasagiline while maintaining specific pharmacokinetic properties.

  • Interleukin-11 Fusion Proteins

    The invention relates to proteins comprising Interleukin 11 (IL-11) (including, but not limited to, fragments and variants thereof), which exhibit thrombopoietic or anti-inflammatory properties, fused to albumin (including, but not limited to, fragments or variants of albumin). These fusion proteins are herein collectively referred to as "albumin fusion proteins of the invention". These fusion proteins exhibit extended shelf-life and/or pharmacokineticproperties and/or extended or therapeutic activity. The invention encompasses therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. The invention also encompasses nucleic acid molecules encoding the albumin fusion proteins of the invention, as well as vectors containing these nucleic acids, host cells transformed with these nucleic acids and vectors, and methods of making the albumin fusion proteins of invention using these nucleic acids, vectors, and/or host cells. The invention also relates to compositions and methods for treatment or prophylaxis of thrombocytopenia or inflammatory diseases.

  • PHARMACOKINETICS OF IONTOPHORETIC SUMATRIPTAN ADMINISTRATION

    Improved pharmacokinetic profiles for the iontophoretic delivery of sumatriptan are described.

  • SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

    Provided are immediate or prolonged administration of certain salts of K.sub.ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K.sub.ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

  • PEPTIDIC GLP-2 AGONISTS

    Novel GLP-2 analogs with improved pharmacokinetic properties are described as well as their use in the treatment of disease.

  • Combination Therapy Comprising A CCR5 Antagonist, A HIV-1 Protease Inhibtior and a Pharmacokinetic Enhancer

    The present invention discloses a novel combination therapy for HIV-1 treatment relying on a combination of at least one CCR5 antagonist, at least one HIV-1 protease inhibitor and at least one pharmacokinetic enhancer of said at least one CCR5 antagonist and/or at least one HIV-1 protease inhibitor. The combination is intended for use in oral treatment of a disorder selected from the group consisting of HIV-1 infection, retroviral infections genetically related to HIV and AIDS, in a treatment-naive patient infected with CCR5 tropic HIV-1 virus.

  • PEGYLATED OPIOIDS WITH LOW POTENTIAL FOR ABUSE AND SIDE EFFECTS

    Provided are methods for reducing the addiction potential and/or reducing one or more CNS-side effects related to the administration of an opioid analgesic drug by administering the opioid analgesic drug in the form of an oligomeric polyethylene glycol conjugate compound. The compounds provided demonstrate notably reduced potential for substance abuse, and possess altered pharmacokinetic profiles relative to the opioid agonists alone, but are not subject to the risk of physical tampering that allows for the recovery and abuse of the opioid agonist associated with certain alternative delivery formulations.

  • ORALLY BIOAVAILABLE PEPTIDE DRUG COMPOSITIONS AND METHODS THEREOF

    The present invention provides orally bioavailable peptide drug compositions including a cyclic peptide and an orally compatible absorption enhancer, as well as methods for providing increased oral bioavailability of peptide drugs.

  • Materials and Methods for Improving Alcohol Metabolism and Alleviating the Effects of Hangovers

    The subject invention provides materials and methods for improving alcohol metabolism in animals. In a preferred embodiment, the invention provides methods for increasing the ability of people to consume alcohol while reducing hangovers or other effects of intoxication. Specifically exemplified herein is the use of a cysteamine compound to reduce the adverse effects of alcohol consumption. For example, the undesirable and unpleasant symptoms association with hangovers can be reduced through consumption, according to the subject invention, of cysteamine hydrochloride.

  • METHOD FOR STABLE AND CONTROLLED DELIVERY OF (-)-HYDROXYCITRIC ACID

    The present invention provides stable encapsulated (-)-hydroxycitric acid ("HCA")-containing compositions and methods of making the same. A method is provided by which the hygroscopic salts of HCA in their relatively pure and active forms, including especially the potassium salt, but also including the sodium salt, are rendered non-hygroscopic and stable (that is, not prone to lactonization, not readily subject to attachment to ligands which inhibit absorption or lead to excretion, and so forth) such that these HCA salts might be included in dry delivery formats, liquid delivery and in controlled-release vehicles. The nonhygroscopic salts of HCA and its derivatives likewise may be protected against acid degradation, lactonization and undesirable ligand binding when exposed to acidic environments or other challenging conditions. The method taught herein can be employed to reduce the polar/ionic qualities of HCA salts and derivatives when presented to the intestinal lumen to provide advantages in absorption.

  • PHARMACOKINETICALLY IMPROVED COMPOUNDS

    A compound of formula A having improved non-specific binding characteristics and pharmacokinetic properties is provided: ##STR00001## or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof.

  • SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

    Provided are immediate or prolonged administration of certain salts of K.sub.ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K.sub.ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

  • POSACONAZOLE INTRAVENOUS SOLUTION FORMULATIONS STABILIZED BY SUBSTITUTED BETA-CYCLODEXTRIN

    The present invention relates to aqueous solutions useful as pharmaceutical compositions of posaconazole for intravenous administration. These compositions include a solubilizing agent, such as a modified .beta.-cyclodextrin in an acidified solution, which can also include a chelating agent such as disodium edetate (EDTA). In clinical trials, a 200 mg posaconazole dose of the selected composition was found to achieve acceptablepharmacokinetic properties.

  • Method for Modulating the Pharmacodynamic Effect of Orally Administered Guanylate Cyclase Receptor Agonists

    A method of modulating the pharmacodynamic effect of a GC-C receptor agonist polypeptide formulation in a subject in need of such treatment is disclosed, The method comprises administering the GC-C receptor agonist polypeptide formulation to the subject before the ingestion of food.

  • TARGETED PRODUCT DISTRIBUTION SYSTEM AND METHOD

    A targeted product distribution system is described herein with respect to an exemplary management of product flow through a distribution center. Specifically, the system and method described herein is directed to the management and display of direct and easily-understood instructions, such that average individuals, as well as those with mental disabilities, will be able to contribute equally to the overall process.

  • AGENT FOR IMPROVING LIPID METABOLISM

    This invention provides an effective means or method for improving lipid metabolism, and a means or method for treatment or prevention of diseases or disorders associated with the lipid metabolism disorder. Specifically, this invention relates to an agent for improving the lipid metabolism comprising, as active ingredients, broken cells of a lactic acid bacterium, and to a method for enhancing an effect of a lactic acid bacterium for improving the lipid metabolism comprising a step of breaking the lactic acid bacterium.

  • TREATMENT OF HYPERTENSION AND/OR PREVENTION OR TREATMENT OF HEART FAILURE IN A MAMMAL RECEIVING ANTI-COAGULANT THERAPY

    The invention relates to methods and pharmaceutical compositions for treating hypertension and/or preventing or treating heart failure in a mammal receiving anti-coagulant therapy using compound(s) which are therapeutically effective but do not impact the pharmacokinetic or the pharmacodynamic effect(s) of the anti-coagulant, such as warfarin.

  • OPTICALLY ACTIVE 2-HYDROXY TETRAHYDROTHIENOPYRIDINE DERIVATIVES, PREPARATION METHOD AND USE IN MANUFACTURE OF MEDICAMENT THEREOF

    Optically active 2-hydroxytetrahydrothienopyridine derivatives represented by Formula I and pharmaceutically acceptable salts, preparation method and use in the manufacture of a medicament thereof are disclosed. Thepharmacodynamic experiment results show that the present compounds of Formula I are useful for inhibiting platelet aggregation. The pharmacokinetic experiment results show that the present compound of Formula I can be converted in vivo into pharmacologically active metabolites and are therefore useful for inhibiting platelet aggregation. Therefore, the present compounds are useful for the manufacture of a medicament for preventing or treating thrombosis and embolism related diseases.

  • METHOD FOR COMPUTING PHARMACOKINETIC PARAMETERS IN MRI

    The present invention relates to a method of dynamic contrast magnetic resonance imaging aimed to improve characterization of tissue image by improving accuracy of computed pharmacokinetic parameters such as K.sup.trans (transfer constant across capillary membrane; a pharmacokinetic parameter of tissue perfusion) using T1W Fast DCE-MRI technique to distinguish between malignant, benign and normal tissues. A phantom and a contrast agent are used in the proposed MRI system for computing accurate T.sub.1 value of a tissue after the contrast is injected based on an intrinsic T.sub.10 value the tissue, wherein the intrinsic T.sub.10 value is adjusted and/or normalized to improve accuracy of the T.sub.1 value computed, which in turn is used for computation of pharmacokinetic parameters at least one of K.sup.trans.

  • TESTOSTERONE GEL AND METHOD OF USE

    The present invention relates to an improved transdermal hydroalcoholic testosterone gen formulation that provides, among other things, a desirable pharmacokinetic hormone profile, and methods of use.

  • SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

    Provided are immediate or prolonged administration of certain salts of K.sub.ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K.sub.ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

  • SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

    Provided are immediate or prolonged administration of certain salts of K.sub.ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K.sub.ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

  • PHARMACOKINETIC DETERMINATION OF INTRAVITREAL AGENTS

    Compositions and methods for evaluating a pharmacokinetic property of an ophthalmic agent administered by intravitreal injection are provided.

  • Systems and Methods for Treating an Opioid-Induced Adverse Pharmacodynamic Response

    Disclosed in certain embodiments is a method of treating or preventing an opioid-induced adverse pharmacodynamic response comprising administering to a patient in need thereof an effective amount of buprenorphine.

  • Intelligent Drug and/or Fluid Delivery System to Optimizing Medical Treatment or Therapy Using Pharmacodynamic and/or Pharamacokinetic Data

    A pharmacodynamic (PD), pharmacokinetic (PK), or both and PK guided infusion device, system and method optimizes the safety and efficacy of various forms of treatment or therapy (e.g., drug and/or fluid) in a variety of health-care and other settings.

  • SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

    Provided are immediate or prolonged administration of certain salts of K.sub.ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K.sub.ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

  • EMULSION FORMULATIONS

    A SEDDS or SMEDDS or SNEDDS formulation for drug delivery of a lipophilic therapeutic agent, providing enhanced modulation of solubility, stability, absorption, metabolism, and/or pharmacokinetic profile of the therapeutic agent by formulation with a lipophilic surfactant, a hydrophilic surfactant, one or more solubilizers and, optionally, digestible oils, resulting in higher bioavailability of the therapeutic agent administered to a subject in need of such therapeutic agent. Also described are pharmaceutical compositions containing the formulations and methods of making and methods of using the formulations and pharmaceutical compositions. Formulations of the disclosure can be constituted to minimize the synthesis of dihydrotestosterone when the therapeutic agent includes testosterone or testosterone esters.

  • RECOMBINANTLY EXPRESSED INSULIN POLYPEPTIDES AND USES THEREOF

    The present disclosure provides recombinantly expressed insulin polypeptides that comprise an N-linked glycan motif. The N-linked glycan motif is not present in wild-type insulins and enables the recombinant expression of glycosylated insulin polypeptides (e.g., in yeast cells). Based on results obtained with synthetic glycosylated insulin conjugates we predict that when these recombinant glycosylated insulin polypeptides are administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the glycosylated insulin polypeptide will be sensitive to serum concentrations of glucose (or an exogenous saccharide such as alpha-methyl mannose). Exemplary insulin polypeptides, polynucleotides encoding these insulin polypeptides, glycosylated insulin polypeptides, pharmaceutical formulations and sustained release formulations are provided in addition to methods of use and preparation.

  • MODULATION OF SOLUBILITY, STABILITY, ABSORPTION, METABOLISM, AND PHARMACOKINETIC PROFILE OF LIPOPHILIC DRUGS BY STEROLS

    A formulation for drug delivery, providing enhanced modulation of solubility, stability, absorption, metabolism, and/or pharmacokinetic profile of a lipophilic therapeutic agent by formulation with sterols and/or sterol esters, resulting in higher bioavailability of a therapeutic agent administered to a subject in need of such therapeutic agent. The formulation contains a therapeutic agent and a sterol or sterol ester, and can, optionally, further contain a solubilizer and/or an enhancing agent. Also described are pharmaceutical compositions containing the formulations and methods of making and methods of using the formulations and pharmaceutical compositions. Formulations of the disclosure can be constituted to minimize the synthesis of dihydrotestosterone when the therapeutic agent includes testosterone or testosterone esters.

  • METHODS AND SYSTEMS USING INTEGRATED METABOLOMICS AND PHARMACOKINETICS FOR MULTI-COMPONENT DRUG EVALUATION

    Disclosed are methods and systems for identifying biochemical changes in a subject in response to administration of a multi-component therapeutic and one or more active ingredients in the multi-component therapeutic. The methods and systems of the invention may be used to elucidate the interaction of the biological system's genome with its environments, and in the pharmacokinetic, pharmacodynamic and toxicology analysis of multi-component therapeutics. The metabolomics methods and systems of the invention can also be used in studies of plant derived agents to demonstrate biochemical alterations in response to the dynamic multi-component intervention.

  • MODULATORS OF PHARMACOKINETIC PROPERTIES OF THERAPEUTICS

    The present application provides for a compound of Formula IV, ##STR00001## or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.

  • Probablistic Pharmacokinetic and Pharmacodynamic Modeling

    The subject matter disclosed herein provides a response to a dose of a substance and/or controls the administration of the dose. In one aspect, there is provided a system. The system may include a processor and at least one memory configured to provide a response determinator. The response determinator may receive therapeutic and wellness data. Moreover, the response determinator may determine a response based on the received therapeutic and wellness data. The response may represent a reaction to a substance integrated with an ingestible event marker. The determined response may be provided to, for example, a therapy controller. Related systems, methods, and articles of manufacture are also described.

  • MARKERS ASSOCIATED WITH CYCLIN-DEPENDENT KINASE INHIBITORS

    The invention provides methods of monitoring differential gene expression of pharmacodynamic (PD) markers in a patient treated with a Cyclin Dependent Kinase Inhibitor (CDKI), methods of determining the sensitivity of a cell to a CDKI by measuring PD markers and methods of screening for candidate CKDI.