Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects |
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| Authors: | Chin?B.?Eap mailto:Chin.Eap@inst.hospvd.ch" title=" Chin.Eap@inst.hospvd.ch" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author,Thierry?Buclin,Elisabeth?Hustert,Gabriela?Bleiber,Kerry?Powell?Golay,Anne-Catherine?Aubert,Pierre?Baumann,Amalio?Telenti,Reinhold?Kerb |
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| Affiliation: | (1) Unit of Biochemistry and Clinical Psychopharmacology, Centre of Psychiatric Neurosciences, University Department of Adult Psychiatry, Hôpital de Cery, 1008 Prilly-Lausanne, Switzerland;(2) Department of Clinical Pharmacology, University Hospital of Lausanne, Switzerland;(3) EPIDAUROS Biotechnologie AG, Am Neuland 1, Bernried, Germany;(4) Division of Infectious Diseases, University Hospital of Lausanne, Switzerland |
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| 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 4OH-midazolam were measured after the oral administration of 7.5 mg or of 75 µg 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 AUCinf values between the different genotypes after the 75-µg or the 7.5-mg dose.Conclusion Presently, CYP3A4 and CYP3A5 genotyping methods do not sufficiently reflect the inter-individual variability of CYP3A activity. |
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| Keywords: | CYP3A4 CYP3A5 Phenotyping |
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