Reduced methylprednisolone clearance causing prolonged pharmacodynamics in a healthy subject was not associated with CYP3A5*3 allele or a change in diet composition.

Journal of Clinical Pharmacology
Su-Jun LeeYuen Yi Hon

Abstract

The influence of diet and genetics was investigated in a healthy white person who had distinctly low methylprednisolone clearance. Pharmacokinetic and pharmacodynamic parameter values were similar on 2 occasions during the consumption of a low-carbohydrate diet and a Weight Watchers diet, indicating that the decreased clearance was unlikely attributable to a change in diet composition. Although the subject was found to be homozygous for CYP3A5*3, genetic findings were not significant for a number of other CYP3A4 and CYP3A5 allelic variants. Because of the high prevalence of CYP3A5*3/*3 in whites and because 5 of 7 white control subjects are also homozygous for CYP3A5*3, this genotype cannot fully explain the reduced metabolism of the drug. Other genetic or contributing factors might have been involved. New polymerase chain reaction-based genotyping methods for functionally defective CYP3A5*6, *8, *9, and *10 alleles were developed in this study. These assays will be useful for CYP3A5 genotype analysis in future clinical studies.

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Citations

Nov 26, 2009·Clinical Neuropharmacology·Anna LoraschiMarco Cosentino
Feb 9, 2010·Pharmacogenomics·Gilbert J Burckart, Shashi Amur
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Sep 28, 2017·Medicine·Silvijus AbramaviciusEdmundas Kadusevicius

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