Efavirenz clearances in vitro and in vivo in six cynomolgus monkeys associated with polymorphic cytochrome P450 2C9 and simulated by individual physiologically based pharmacokinetic models
| Autor: | Shotaro Uehara, Tomonori Miura, Yasuhiro Uno, Makiko Shimizu, Masahiro Utoh, Hiroshi Yamazaki, Takashi Kusama |
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| Rok vydání: | 2017 |
| Předmět: |
Cyclopropanes
Male Physiologically based pharmacokinetic modelling Efavirenz Cytochrome P-450 CYP2C9 Inhibitors Genotype Pharmaceutical Science Pharmacology Biology 030226 pharmacology & pharmacy Models Biological 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics In vivo Animals Pharmacology (medical) Computer Simulation CYP2C9 Cytochrome P-450 CYP2C9 Polymorphism Genetic Heterozygote advantage General Medicine In vitro Benzoxazines Macaca fascicularis chemistry Liver 030220 oncology & carcinogenesis Alkynes Microsome Microsomes Liver |
| Zdroj: | Biopharmaceuticsdrug disposition. 38(7) |
| ISSN: | 1099-081X |
| Popis: | Cynomolgus monkey cytochrome P450 2C9 (formerly known as P450 2C43) variation was reportedly associated with metabolic clearance of the antiretroviral drug efavirenz in vivo (in three wild-type, one heterozygote and two homozygote animals), being unlikely in the case of human P450 2B6-dependent efavirenz clearance. In this study, the liver microsomal elimination rates of efavirenz for the same individual animals previously treated with intravenous/oral administrations of efavirenz showed significant reductions associated with the P450 2C9 p.[(I112L)] genotype (p |
| Databáze: | OpenAIRE |
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