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Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects

2004; Springer Science+Business Media; Volume: 60; Issue: 4 Linguagem: Inglês

10.1007/s00228-004-0767-7

1432-1041

Chin B. Eap, Thierry Buclin, Elisabeth Hustert, Gabriela Bleiber, KerryPowell Golay, Anne-Catherine Aubert, Pierre Baumann, Amalio Telenti, Reinhold Kerb,

Pharmacological Effects and Toxicity Studies

We investigated whether differences in pharmacokinetics of midazolam, a CYP3A probe, could be demonstrated between subjects with different CYP3A4 and CYP3A5 genotypes. 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 µg of midazolam in 21 healthy subjects. 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 AUCinf values between the different genotypes after the 75-µg or the 7.5-mg dose. Presently, CYP3A4 and CYP3A5 genotyping methods do not sufficiently reflect the inter-individual variability of CYP3A activity.