Current Issue : January - March Volume : 2015 Issue Number : 1 Articles : 5 Articles
Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of\nneuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study\naims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely,\nYin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and\nto reveal the underlined mechanisms. It was found that although ????max, AUC and urinary recovery of OC, as well as metabolic\nratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in\nrat studies (P < 0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related\nparameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to\nenhance viral inhibition of OA (P < 0.01). In summary, although there was potential interaction between OA and CMF1 found\nin rat studies, its clinical impact was expected to be minimal.The coadministration of OA and CMF1 at the clinical recommended\ndosages is, therefore, considered to be safe....
The present study was carried out to study the effects of Rhododendron arboreum extract on pharmacokinetic of isradipine in rats. Albino wistar rats (200-250 g) were used for pharmacokinetic study. Rats were divided into three groups. Group I were treated with only isradipine (1 mg/kg, p.o.). Group 2 and 3 were treated with Rhododendron arboreum extract (RAE) (100 and 200 mg/kg, p.o., respectively) 15 minute before administration of isradipine (1 mg/kg, p.o). Blood samples were collected at different time intervals from each animal. Plasma was separated from blood. Plasma concentrations of isradipine were measured by HPLC method. Pharmacokinetic parameters such as area under curve (AUC), peak plasma concentration (Cmax), time to occur peak plasma concentration (Tmax) and half-life (T1/2) were calculated. Animals were treated with RAE followed by isradipine significantly (P<0.05) increased AUC as compared to animals treated with only isradipine. The Cmax of Isradipine without and with RAE (100 and 200 mg/kg) was found to be 2044±9.945 ng/l, 3060.5±12.29 ng/l and 387.06±1.37 ng/l respectively. Tmax of isradipine without and with RAE (100 and 200 mg/kg) was found to be 1 and 2 hrs respectively. The half-life of isradipine without and with RAE (100 and 200 mg/kg) was found to be 6.18±0.091, 7.46±0.097 and 8.41±0.147 respectively. Cmax, Tmax and AUC after oral administration of isradipine were significantly increased by simultaneous oral treatment with RAE respectively. The results of present investigation showed that RAE significantly increased bioavailability of isradipine on dose depended manner....
Background: Interferon (IFN) alpha conjugation to polyethylene glycol (PEG) results in a better pharmacokinetic\nprofile and efficacy. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety\nproperties of a new, locally developed, 40-kDa PEG-IFN alpha-2b preparation with a reference, commercially\navailable PEG-IFN alpha-2a in healthy male volunteers.\nMethods: A randomized, crossover, double-blind study with a 3-weeks washout period, was done. A single 180\nmicrograms PEG-IFN alpha-2 dose was administered subcutaneously in both groups. Sixteen apparently healthy\nmale subjects were included. Serum PEG-IFN concentration was measured during 336 hours by an enzyme\nimmunoassay (EIA). Other clinical and laboratory variables were used as pharmacodynamic and safety criteria.\nResults: The pharmacokinetic comparison by EIA yielded a high similitude between the formulations. In spite of a\nhigh subject variability, the parameters� mean were very close (in all cases p > 0.05): AUC: 53623 vs. 44311 pg.h/mL;\nCmax: 333 vs. 271 pg/mL; Tmax: 54 vs. 55 h; half-life (t1/2): 72.4 vs. 64.8 h; terminal elimination rate (lambda): 0.011\nvs. 0.014 h-1; mean residence time (MRT): 135 vs. 123 h for reference and study preparations, respectively. There\nwere no significant differences with respect to the pharmacodynamic variables either: serum neopterin and beta-2\nmicroglobulin levels, stimulation of 2�5� oligoadenylate synthetase expression, and serum IFN antiviral activity. A\nstrong Spearman�s rank order correlation (p < 0.01) between the pharmacokinetic and pharmacodynamic\nconcentration-time curves was observed. Both products caused similar leukocyte counts diminution and had similar\nsafety profiles. The most frequent adverse reactions were leukopenia, fever, thrombocytopenia, transaminases\nincrease and asthenia, mostly mild.\nConclusions: Both formulations are fully comparable from the pharmacokinetic, pharmacodynamic, and safety\nprofiles. Efficacy trials can be carried out to confirm clinical similarity....
Purpose Retinoblastoma is a childhood cancer of the retina.\nClinical trials have shown that local delivery of broad spectrum\nchemotherapeutic agents is efficacious. Recent studies characterizing\nthe genomic and epigenomic landscape of retinoblastoma\nidentified spleen tyrosine kinase (SYK) as a promising candidate for\ntargeted therapy. The purpose of this study was to conduct\npreclinical testing of the SYK antagonist R406 to evaluate it as a\ncandidate for retinoblastoma treatment.\nMethods The efficacy of the SYK antagonist R406 delivered\nlocally in a human orthotopic xenograft mouse model of retinoblastoma\nwas tested. Intraocular exposure of R406 was determined\nfor various routes and formulations.\nResults There was no evidence of efficacy for subconjunctival.\nR406. Maximal vitreal concentration was 10-fold lower than the\nminimal concentration required to kill retinoblastoma cells in vitro.\nDosage of R406 subconjunctivally from emulsion or suspension\nformulations, direct intravitreal injection of the\nsoluble prodrug of R406 (R788), and repeated topical\nadministration of R406 all increased vitreal exposure, but\nfailed to reach the exposure required for retinoblastoma cell death\nin culture.\nConclusion Taken together, these data suggest that R406 is not a\nviable clinical candidate for the treatment of retinoblastoma. This\nstudy highlights the importance of pharmacokinetic testing of\nmolecular targeted retinoblastoma therapeutics....
An effective method of construction of a linear\nestimator of AUC in the finite interval, optimal in the\nminimax sense, is developed and demonstrated for five PK\nmodels. The models may be given as an explicit C(t) relationship\nor defined by differential equations. For high\nvariability and rich sampling the optimal method is only\nmoderately advantageous over optimal trapezoid or standard\nnumerical approaches (Gauss-Legendre or Clenshaw-\nCurtis quadratures). The difference between the optimal\nestimator and other methods becomes more pronounced\nwith a decrease in sample size or decrease in the variability.\nThe described estimation method may appear useful\nin development of limited-sampling strategies for AUC\ndetermination, as an alternative to the widely used\nregression-based approach. It is indicated that many alternative\napproaches are also possible....
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