کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2474460 1113141 2016 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites
ترجمه فارسی عنوان
مطالعه فارماکوکینتیک داخل سلولی zidovudine و متابولیت های فسفریله آن
کلمات کلیدی
LC-MS / MS؛ زیدوودین؛ متابولیت ها؛ فسفات؛ hPBMCs؛ hPBMCs؛ فارماکوکینتیک؛ جنبشی داخل سلولی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5′-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.

A pharmacokinetic experiment has been performed to evaluate the pharmacokinetics of zidovudine in plasma and pharmacokinetics of zidovudine and its phosphate metabolites in human peripheral blood mononuclear cells.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Acta Pharmaceutica Sinica B - Volume 6, Issue 2, March 2016, Pages 158–162
نویسندگان
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