Related Experiment Video
Updated: Aug 15, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
Pharmacokinetics and pharmacodynamics of etizolam are influenced by polymorphic CYP2C19 activity
T Fukasawa1, N Yasui-Furukori, A Suzuki
1Department of Psychiatry, Yamagata University School of Medicine, 990-9585 Yamagata, Japan. tfukasaw@med.id.yamagata-u.ac.jp
Objective:
To examine the effect of cytochrome P450 (CYP) 2C19 activity on the single-dose pharmacokinetics and pharmacodynamics of etizolam.
Methods:
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.
Results:
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).
Conclusion:
The present study suggests that the single-dose pharmacokinetics and pharmacodynamics of etizolam are influenced by polymorphic CYP2C19 activity.
Related Concept Videos
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Drug toxicity: Idiosyncratic Reactions
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase