Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects

被引：82

作者：

Eap, CB ^{[1
]}

Buclin, T

Hustert, E

Bleiber, G

Golay, KP

Aubert, AC

Baumann, P

Telenti, A

Kerb, R

机构：

[1] Hop Cery, Univ Dept Adult Psychiat, Unit Biochem & Clin Psychopharmacol, CH-1008 Prilly, Switzerland

[2] Univ Lausanne Hosp, Dept Clin Pharmacol, Lausanne, Switzerland

[3] EPIDAUROS Biotechnol AG, Bernried, Germany

[4] Univ Lausanne Hosp, Div Infect Dis, Lausanne, Switzerland

来源：

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY | 2004年 / 60卷 / 04期

关键词：

CYP3A4; CYP3A5; phenotyping;

D O I：

10.1007/s00228-004-0767-7

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Objective. We investigated whether differences in pharmacokinetics of midazolam, a CYP3A probe, could be demonstrated between subjects with different CYP3A4 and CYP3A5 genotypes. Methods. Plasma concentrations of midazolam, and of total (conjugated + unconjugated) 1'OH-midazolam, and 4'OH-midazolam were measured after the oral administration of 7.5 mg or of 75 mug of midazolam in 21 healthy subjects. Results. CYP3A5*7, CYP3A4*1E, CYP3A4*2, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*8, CYP3A4*11, CYP3A4*12, CYP3A4*13, CYP3A4*17 and CYP3A4*18 alleles were not identified in the 21 subjects. CYP3A5*3, CYP3A5*6, CYP3A4*1B and CYP3A4*1F alleles were identified in 20, 1, 4 and 2 subjects, respectively. No statistically significant differences were observed for the AUC(inf) values between the different genotypes after the 75-mug or the 7.5-mg dose. Conclusion. Presently, CYP3A4 and CYP3A5 genotyping methods do not sufficiently reflect the inter-individual variability of CYP3A activity.

引用

页码：231 / 236

页数：6

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