当前位置： SCI文献检索 > PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY期刊下所有文献 > Effects of the CYP2C19 genotype and cigarette smoking on the single oral dose pharmacokinetics and pharmacodynamics of estazolam.

Effects of the CYP2C19 genotype and cigarette smoking on the single oral dose pharmacokinetics and pharmacodynamics of estazolam.

Abstract：

:The effects of the cytochrome P450 (CYP)2C19 genotype and cigarette smoking on the single oral dose pharmacokinetics and pharmacodynamics of estazolam were studied in 16 healthy male volunteers. The two mutated alleles (CYP2C19*2 and CYP2C19*3) causing absent CYP2C19 activity were identified by PCR-based restriction enzyme analysis. Five subjects had no mutated allele, five had one mutated allele, and six had two mutated alleles. Seven subjects were smokers, and nine were nonsmokers. The subjects received a single oral 4-mg dose of estazolam, and blood samplings and evaluation of psychomotor function were conducted up to 72 h after dosing. There was no significant difference among the groups with no, one, and two mutated alleles for the peak plasma concentration (145.2+/-36.5 vs. 142.1+/-33.6 vs. 113.2+/-29.7 ng/ml), area under the plasma concentration-time curve (0- infinity ) (4916.0+/-1276.4 vs. 4389.6+/-736.1 vs. 4047.3+/-613.8 ng x h/ml), apparent oral clearance (0.22+/-0.05 vs. 0.25+/-0.03 vs. 0.25+/-0.03 ml/min/kg), and elimination half-life (24.4+/-4.6 vs. 29.6+/-8.5 vs. 30.7+/-3.9 h). Similarly, none of the pharmacokinetic parameters was significantly different between the nonsmoker and smoker groups. Neither the number of mutated allele nor cigarette smoking affected the psychomotor function parameters significantly. The present study suggests that neither the CYP2C19 genotype nor cigarette smoking affects the single oral dose pharmacokinetics and pharmacodynamics of estazolam.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Aoshima T,Fukasawa T,Otsuji Y,Okuyama N,Gerstenberg G,Miura M,Ohkubo T,Sugawara K,Otani K

doi

10.1016/S0278-5846(02)00357-3

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

535-8

issue

3

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(02)00357-3

journal_volume

27

pub_type

杂志文章

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