Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines.
Pharmacogenetic studies have shown that several cytochrome P450 (CYP) enzymes exhibit genetic polymorphisms. Several benzodiazepines (BZPs) are metabolized predominantly or partly by polymorphic CYP2C19 and CYP3A4/5. The pharmacokinetics of diazepam, etizolam, quazepam and desmethylclobazam have been shown to be affected by CYP2C19 polymorphism. The CYP3A5 polymorphism has been reported to affect the pharmacokinetics of alprazolam, but its effect on midazolam kinetics has been inconclusive. For etizolam and desmethylclobazam, some data suggest that CYP2C19 deficiency leads to side-effects or toxicity. For the remaining BZPs the clinical significance of the observed pharmacokinetic changes remains unclear. Further studies on the effects of genetic polymorphisms of CYP enzymes on the pharmacokinetics and pharmacodynamics of BZPs are necessary to guide treatment individualization and optimization.
Fukasawa
T
T
Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan. tfukasaw@med.id.yamagata-u.ac.jp
Suzuki
A
A
Otani
K
K
D001189:Aryl Hydrocarbon Hydroxylases; D001569:Benzodiazepines / Q000493:pharmacokinetics* / Q000494:pharmacology; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D001569:Benzodiazepines; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human