Current Issue : July - September Volume : 2018 Issue Number : 3 Articles : 5 Articles
Context: The assessment absolute bioavailability of oral hydrocortisone is complicated by its saturable binding to cortisol binding globulin (CBG). Previous assessment of bioavailability used a cortisol radioimmunoassay which has cross reactivity with other steroids. Salivary cortisone is a measure of free cortisol and LC-MS/MS is the gold standard method for measuring steroids. We here report the absolute bioavailability of hydrocortisone calculated using serum cortisol and salivary cortisone measured by LC-MS/MS.\n\nMethods: 14 healthy male dexamethasone suppressed volunteers were administered 20 mg hydrocortisone either intravenously or orally by tablet. Samples of serum and saliva were taken and measured for cortisol and cortisone by LC-MS/MS. Serum cortisol was corrected for saturable binding using published data and pharmacokinetic parameters derived using the program WinNonlin.\n\nResults: The mean (95% CI) bioavailability of oral hydrocortisone calculated from serum cortisol, unbound serum cortisol and salivary cortisone was 1.00 (0.89-1.14); 0.88 (0.75-1.05); and 0.93 (0.83-1.05), respectively.\n\nConclusion: The data confirm that, after oral administration, hydrocortisone is completely absorbed. The data derived from serum cortisol corrected for protein binding, and that from salivary cortisone, are similar supporting the concept that salivary cortisone reflects serum free cortisol levels and that salivary cortisone can be used as a non-invasive method for measuring the pharmacokinetics of hydrocortisone....
A biosimilar is a biologic product that is highly similar to a licensed biologic (ââ?¬Å?originatorââ?¬Â) such that there are no clinically\nmeaningful differences in safety, purity, or potency between the biosimilar and the originator. As patent protection and data\nexclusivity for the biologic rituximab expire, several potential biosimilars to rituximab are in development, which could soon lead to\nthe availability of numerous rituximab biosimilars. Biosimilars are evaluated using thorough and rigorous analyses of the potential\nbiosimilar versus the originator biological to confirm similar structure, function, and clinical efficacy as well as safety. Approval of\na biosimilar is based upon the totality of the evidence demonstrating similarity to the originator. An understanding of the process\nof the interchangeable designation of a biosimilar is important in the context of patient outcomes. We conducted an analysis of\nthe properties and benefits of rituximab in the treatment of inflammatory diseases, the development and approval of biosimilars,\nand the potential benefits of rituximab biosimilars. PubMed and ClinicalTrials.gov databases were searched for ââ?¬Å?biosimilarââ?¬Â and\nââ?¬Å?rituximabââ?¬Â and regulatory and pharmaceutical company web pages were screened regarding biosimilars in development and\nspecific guidelines developed for the approval of biosimilars.The results indicate that, at present, six rituximab biosimilar candidates\nare undergoing comparative clinical development, and two were recently approved in the European Union. Our analysis indicates\nrituximab biosimilars are expected to have a continuing role in treating inflammatory conditions such as rheumatoid arthritis....
The increasing availability of biosimilar medicines in Middle Eastern regions may provide an opportunity to increase the number\nof rheumatology patients who have access to traditionally more expensive biologicmedicines. However, as well as a lack of realworld\ndata on the use of biosimilar medicines in practice, the availability of intended copies in the region may undermine\nphysician confidence in prescribing legitimate biosimilar medicines. There is a need for regional recommendations for healthcare\nprofessionals to ensure that biosimilar drugs can be used safely. Therefore, a literature search was performed with the aim of\nproviding important recommendations for the regulation and use of biosimilar medicines in the Middle East from key opinion\nleaders in rheumatology fromthe region. These recommendations focus on improving the availability of relevant real-world data,\nensuring that physicians are aware of the difference between intended copies and true biosimilars and ensuring that physicians are\nresponsible for making any prescribing and switching decisions....
Relative biodistribution of FDA-approved innovator and generic sodium ferric gluconate\n(SFG) drug products was investigated to identify differences in tissue distribution of iron after\nintravenous dosing to rats. Three equal cohorts of 42 male Sprague-Dawley rats were created with\neach cohort receiving one of three treatments: (1) the innovator SFG product dosed intravenously\nat a concentration of 40 mg/kg; (2) the generic SFG product dosed intravenously at a concentration\nof 40 mg/kg; (3) saline dosed intravenously at equivalent volume to SFG products. Sampling\ntime points were 15 min, 1 h, 8 h, 1 week, two weeks, four weeks, and six weeks post-treatment.\nSix rats from each group were sacrificed at each time point. Serum, femoral bone marrow, lungs,\nbrain, heart, kidneys, liver, and spleen were harvested and evaluated for total iron concentration by\nICP-MS. The ICP-MS analytical method was validated with linearity, range, accuracy, and precision.\nResults were determined for mean iron concentrations (�¼g/g) and mean total iron (whole tissue)\ncontent (�¼g/tissue) for each tissue of all groups at each time point. A percent of total distribution\nto each tissue was calculated for both products. At any given time point, the overall percent iron\nconcentration distribution did not vary between the two SFG drugs by more than 7% in any tissue.\nOverall, this study demonstrated similar tissue biodistribution for the two SFG products in the\nexamined tissues....
Snake venoms are sources of molecules with proven and potential therapeutic applications.\nHowever, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive,\nedematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain\nunknown. Using functional genomics coupled to the connectivity map (C-map) approach, we\nundertook a wide range indirect search for biological activities within the venom of the South\nAmerican pit viper Bothrops jararaca. For that effect, venom was incubated with human breast\nadenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list\nof 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern\nrecognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive,\nantimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported\nfor B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity;\n(2) treatment of neuropsychiatric illnesses (Parkinson�s disease, schizophrenia, depression, and\nepilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map\nresults also indicated that B. jararaca venom may have components that target G-protein-coupled\nreceptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion\nchannels. Although validation experiments are still necessary, the C-map correlation to drugs with\nactivities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum\napproach for biological activity screening, and rekindles the snake venom-based search for new\ntherapeutic agents....
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