کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484996 | 1114342 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacokinetics and Metabolism of SRX246: A Potent and Selective Vasopressin 1a Antagonist
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کلمات کلیدی
Serum protein binding - اتصال پروتئین سرمPTSD - اختلال استرسی پس از ضایعه روانیIntermittent explosive disorder - اختلال انفجاری متناوبMajor depression - افسردگی شدیدclearance - ترخیص کالا از گمرکPharmacokinetics - فارماکوکینتیکBioavailability - فراهم زیستیMetabolism - متابولیسم Permeability - نفوذپذیری
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The compound previously showed efficacy in animal models of mood disorders and excellent safety and tolerability in healthy volunteers in phase I clinical trials. In this study, SRX246 was further characterized in rats and dogs. In vitro determinations of permeability, protein binding, hepatocyte metabolism, and cytochrome P450 enzyme inhibition and in vivo assessments of pharmacokinetics were conducted. In parallel artificial membrane permeability assay (PAMPA) and PAMPA-blood-brain barrier models, SRX246 was comparable to highly permeable, orally active pharmaceuticals. SRX246 hydrochloride salt was 95.5 ± 1.7%, 95.9 ± 1.3%, and 98.6 ± 0.4% bound to rat, dog, and human serum proteins, respectively, and was stable in serum after a 4 h incubation at 37°C. P450 enzyme inhibition results showed a very low potential for drug-drug interactions. Metabolism in primary hepatocytes demonstrated that SRX246 was stable in humans and moderately metabolized in dogs and rats. Plasma pharmacokinetics findings showed a half-life (T1/2) of 2 and 6 h in rat and dog, respectively. Rat brain levels following a single oral dose were approximately 20% of plasma values with a T1/2 of 6 h. The observed profile for SRX246 supports further development. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2033-2043, 2013
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 6, June 2013, Pages 2033-2043
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 6, June 2013, Pages 2033-2043
نویسندگان
Karine M. Fabio, Christophe D. Guillon, Shi-Fang Lu, Ned D. Heindel, Michael J. Brownstein, Carl J. Lacey, Carrie Garippa, Neal G. Simon,