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Reduced Methylprednisolone Clearance Causing Prolonged Pharmacodynamics in a Healthy Subject Was Not Associated With CYP3A5 * 3 Allele or a Change in Diet Composition
Author(s) -
Lee SuJun,
Jusko William J.,
Salaita Christine G.,
Calis Karim A.,
Jann Michael W.,
Spratlin Vicky E.,
Goldstein Joyce A.,
Hon Yuen Yi
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006287588
Subject(s) - pharmacodynamics , allele , genotype , genotyping , cyp3a5 , biology , pharmacokinetics , pharmacogenetics , medicine , pharmacology , endocrinology , genetics , gene
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 .