Pharmacokinetics and pharmacodynamics of etizolam are influenced by polymorphic CYP2C19 activity

• DOI: 10.1007/s00228-005-0032-8
• Publication Date: 2005-10-31T13:36:31Z
• Authors: T. Fukasawa; N. Yasui–Furukori; A. Suzuki; Y. Inoue; T. Tateishi; K. Otani
• Keywords: Pharmacodynamics

To examine the effect of cytochrome P450 (CYP) 2C19 activity on the single-dose pharmacokinetics and pharmacodynamics of etizolam.The subjects were 21 healthy Japanese volunteers. The two mutated alleles (CYP2C19*2 and CYP2C19*3) causing absent CYP2C19 activity were identified by a polymerase chain reaction method. Twelve subjects were extensive metabolizers (EMs) with no or one mutated allele, and nine subjects were poor metabolizers (PMs) with two mutated alleles. The subjects received a single oral 1-mg dose of etizolam, and blood samplings and evaluation of psychomotor function were conducted up to 24 h after dosing.The PMs had significantly larger total area under the plasma concentration-time curve (287+/-74 vs 178+/-122 ng.h/ml, p<0.05) and longer elimination half-life (14.8+/-4.2 vs 10.5+/-3.9 h, p<0.05) of etizolam than the EMs. The area under the score-time curve from 0 to 8 h of the Stanford Sleepiness Scale was significantly larger in the PMs than in EMs (28.9+/-5.2 vs 22.9+/-6.9 score.h, p<0.05).The present study suggests that the single-dose pharmacokinetics and pharmacodynamics of etizolam are influenced by polymorphic CYP2C19 activity.