Current Issue : April - June Volume : 2017 Issue Number : 2 Articles : 6 Articles
The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of puerarin loaded carboxymethyl chitosan\nmicrospheres (Pue-CCMs). The differences in pharmacokinetics parameters of rats after intragastric administration of Pue-CCMs\nand puerarin were investigated using HPLC. To assess the protective effect of Pue-CCMs on myocardial injury in rats, serum\nlevels of creatine kinase (CK), lactate dehydrogenase (LDH), total superoxide dismutase (T-SOD), and malondialdehyde (MDA)\nwere measured, in addition to pathological examinations and immunohistochemical staining. Our present study has shown that\nthe AUC0ââ?¬â??...
In addition to its well-known abortifacient effect, mifepristone (MIF) has been used as an anticancer drug for various cancers in\nmany studies with an in-depth understanding of the mechanism of action. However, application of MIF is limited by its poor water\nsolubility and low oral bioavailability. In this work, we developed a drug delivery system based on chitosan nanoparticles (CNs) to\nimprove its bioavailability and anticancer activity. The MIF-loaded chitosan nanoparticles (MCNs) were prepared by convenient\nionic gelation techniques between chitosan (Cs) and tripolyphosphate (TPP). The preparation conditions, including Cs concentration,\nTPP concentration, Cs/MIF mass ratio, and pH value of the TPP solution, were optimized to gain better encapsulation efficiency\n(EE) and drug loading capacity (DL). MCNs prepared with the optimum conditions resulted in spherical particles with an\naverage size of 200 nm. FTIR and XRD spectra verified that MIF was successfully encapsulated in CNs. The EE and DL of MCNs\ndetermined by HPLC were 86.6% and 43.3%, respectively. The in vitro release kinetics demonstrated that MIF was released from\nCNs in a sustained-release manner. Compared with free MIF, MCNs demonstrated increased anticancer activity in several cancer\ncell lines. Pharmacokinetic studies in male rats that were orally administered MCNs showed a 3.2-fold increase in the area under\nthe curve from 0 to 24 h compared with free MIF. These results demonstrated that MCNs could be developed as a potential delivery\nsystem for MIF to improve its anticancer activity and bioavailability....
Background: Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected\nin critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy\n(CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter\nchanges observed in critically ill septic patients with AKI, who are on CRRT.\nMethod: Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred\nreporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological\nquality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients\nwith AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the\nCRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported.\nResults: Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53\ntreatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off\nmembranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst\nthe studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2ââ?¬â??2.3 L/h for CVVH,\n0.9ââ?¬â??2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported.\nThe optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with\nan MIC of 4 mg/L in one study only.\nConclusions: Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with\nAKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in\nthese patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug\nmonitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research\nsettings....
Background: Lucerastat, an inhibitor of glucosylceramide synthase, has the potential to restore the balance\nbetween synthesis and degradation of glycosphingolipids in glycolipid storage disorders such as Gaucher disease\nand Fabry disease. The safety, tolerability, and pharmacokinetics of oral lucerastat were evaluated in two separate\nrandomized, double-blind, placebo-controlled, single- and multiple-ascending dose studies (SAD and MAD, respectively)\nin healthy male subjects.\nMethods: In the SAD study, 31 subjects received placebo or a single oral dose of 100, 300, 500, or 1000 mg lucerastat.\nEight additional subjects received two doses of 1000 mg lucerastat or placebo separated by 12 h. In the MAD study,\n37 subjects received placebo or 200, 500, or 1000 mg b.i.d. lucerastat for 7 consecutive days. Six subjects in\nthe 500 mg cohort received lucerastat in both absence and presence of food.\nResults: In the SAD study, 15 adverse events (AEs) were reported in ten subjects. Eighteen AEs were reported\nin 15 subjects in the MAD study, in which the 500 mg dose cohort was repeated because of elevated\nalanine aminotransferase (ALT) values in 4 subjects, not observed in other dose cohorts. No severe or serious\nAE was observed. No clinically relevant abnormalities regarding vital signs and 12ââ?¬â??lead electrocardiograms\nwere observed. Lucerastat Cmax values were comparable between studies, with geometric mean Cmax 10.5\n(95% CI: 7.5, 14.7) and 11.1 (95% CI: 8.7, 14.2) Ã?¼g/mL in the SAD and MAD study, respectively, after 1000 mg\nlucerastat b.i.d. tmax (0.5 ââ?¬â?? 4 h) and t1/2 (3.6 ââ?¬â?? 8.1 h) were also within the same range across dose groups in\nboth studies. Using the Gough power model, dose proportionality was confirmed in the SAD study for Cmax\nand AUC0ââ?¬â??âË?ž, and for AUC0 ââ?¬â??12 in the MAD study. Fed-to-fasted geometric mean ratio for AUC0ââ?¬â??12 was 0.93\n(90% CI: 0.80, 1.07) and tmax was the same with or without food, indicating no food effect.\nConclusions: Incidence of drug-related AEs did not increase with dose. No serious AEs were reported for any\nsubject. Overall, lucerastat was well tolerated. These results warrant further investigation of substrate reduction\ntherapy with lucerastat in patients with glycolipid storage disorders....
Recent meta-analyses and publications over the past 15 years have provided evidence\nshowing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout\nthis time, there have not been any research articles proposing a gender stratified dose-adjustment\nresulting in an equivalent total drug exposure. Metoprolol pharmacokinetic data was obtained\nfrom a previous publication. Data was modeled using nonlinear mixed effect modeling using the\nMONOLIX software package to quantify metoprolol concentrationââ?¬â??time data. Gender-stratified\ndosing simulations were conducted to identify equivalent total drug exposure based on a 100 mg\ndose in adults. Based on the pharmacokinetic modeling and simulations, a 50 mg dose in adult\nwomen provides an approximately similar metoprolol drug exposure to a 100 mg dose in adult men....
Background: Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading\nglycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent\nan alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous\nadministration.\nMethods: Adults receiving teicoplanin for S. aureus BJI were included in a retrospective cohort study investigating\nintravenous or subcutaneous teicoplanin safety and pharmacokinetics.\nResults: Sixty-five S. aureus BJIs (orthopedic device-related infections, 69 %; methicillin-resistance, 17 %) were\ntreated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7ââ?¬â??6.5) after a loading dose of 5 injections 12 h\napart. The first trough teicoplanin level (Cmin) reached the therapeutic target (15 mg/L) in 26 % of patients, only. An\noverdose (Cmin >25 mg/L) was observed in 16 % patients, 50 % of which had chronic renal failure (p = 0.049). Seven\nadverse events occurred in 6 patients (10 %); no predictive factor could be highlighted. After a 91-week follow-up\n(IQR, 51ââ?¬â??183), 27 treatment failures were observed (42 %), associated with diabetes (OR, 5.1; p = 0.057), systemic\ninflammatory disease (OR, 5.6; p = 0.043), and abscess (OR, 4.1; p < 10âË?â??3). A normal CRP-value at 1 month was\nprotective (OR, 0.2; p = 0.029). Subcutaneous administration (n = 14) showed no difference in pharmacokinetics and\ntolerance compared to the intravenous route.\nConclusions: Teicoplanin constitutes a well-tolerated therapeutic alternative in S. aureus BJI, with a possible\nsubcutaneous administration in outpatients. The loading dose might be increase to 9ââ?¬â??12 mg/kg to quickly reach\nthe therapeutic target, but tolerance of such higher doses remains to be evaluated, especially if using the\nsubcutaneous route....
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