کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513836 | 1556500 | 2017 | 25 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Population Approach to Efavirenz Therapy
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Efavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor commonly used as first-line therapy in the treatment of human immunodeficiency virus (HIV), with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady-state plasma concentrations, a population pharmacokinetic model was developed from 96 HIV-positive individuals, using a nonlinear mixed-effect method with Monolix® software. A one-compartment with first-order absorption and elimination model adequately described the data. To explain between-subject variability, demographic characteristics, biochemical parameters, hepatitis C virus-HIV coinfection, and genetic polymorphisms were tested. A combination of the single-nucleotide polymorphisms rs2279343 and rs3745274, both in the CYP2B6 gene, were the only covariates influencing clearance, included in the final model. Oral clearance was estimated to be 19.6 L/h, 14.15 L/h, and 6.08 L/h for wild-type, heterozygous mutated and homozygous mutated individuals, respectively. These results are in accordance with the current knowledge of EFV metabolism and also suggest that in homozygous mutated individuals, a dose adjustment is necessary. Hepatitis C virus-HIV coinfection does not seem to be a predictive indicator of EFV pharmacokinetic disposition.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 10, October 2017, Pages 3161-3166
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 10, October 2017, Pages 3161-3166
نویسندگان
Hélder Duarte, João Paulo Cruz, Natália Aniceto, Ana Clara Ribeiro, Ana Fernandes, Paulo Paixão, Francisco Antunes, José Morais,