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Eur J Clin Pharmacol. 2004 Jun;60(4):231-6. Epub 2004 Apr 28.

Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects.

Author information

1
Unit of Biochemistry and Clinical Psychopharmacology, Centre of Psychiatric Neurosciences, University Department of Adult Psychiatry, Hôpital de Cery, 1008 Prilly-Lausanne, Switzerland. Chin.Eap@inst.hospvd.ch

Abstract

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 micro g 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- micro g or the 7.5-mg dose.

CONCLUSION:

Presently, CYP3A4 and CYP3A5 genotyping methods do not sufficiently reflect the inter-individual variability of CYP3A activity.

PMID:
15114431
DOI:
10.1007/s00228-004-0767-7
[Indexed for MEDLINE]

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