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- W2113247918 abstract "Background & aim:In vitro studies have identified both midazolam and tacrolimus as dual CYP3A4 and CYP3A5 substrates. In vivo; however, the CYP3A5 genotype has a marked impact on tacrolimus pharmacokinetics, whereas it seems not to affect midazolam pharmacokinetics. The aim of the current study was to explore this paradigm in a relevant clinical setting. Patients & methods: A case–control study in 80 tacrolimus-treated renal transplant recipients comparing systemic and apparent oral midazolam clearance and tacrolimus pharmacokinetics in CYP3A5 expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (CYP3A5*3/*3) was performed. Results: CYP3A5 expressers display an approximately 2.4-fold higher tacrolimus clearance as compared with CYP3A5 nonexpressers, whereas there are no differences in systemic and apparent oral midazolam clearance. Conclusion: These data confirm that in vivo CYP3A5 plays an important role in tacrolimus metabolism, while its contribution to midazolam metabolism in a relevant study population is limited. Furthermore, these data suggest that midazolam is to be considered as a phenotypic probe for in vivo CYP3A4 activity rather than combined CYP3A4 and CYP3A5 activity. Original submitted 12 March 2013; Revision submitted 10 July 2013" @default.
- W2113247918 created "2016-06-24" @default.
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- W2113247918 date "2013-09-01" @default.
- W2113247918 modified "2023-09-25" @default.
- W2113247918 title "Impact of <i>CYP3A5</i> genotype on tacrolimus versus midazolam clearance in renal transplant recipients: new insights in CYP3A5-mediated drug metabolism" @default.
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- W2113247918 doi "https://doi.org/10.2217/pgs.13.133" @default.
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