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

Su Jun Lee, William J. Jusko, Christine G. Salaita, Karim A. Calis, Michael W. Jann, Vicky E. Spratlin, Joyce A. Goldstein, Yi Hon Yuen

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)515-526
Number of pages12
JournalJournal of Clinical Pharmacology
Volume46
Issue number5
DOIs
StatePublished - May 1 2006

Keywords

  • CYP3A5*3 allele
  • Genotyping method
  • Low-carbohydrate diet
  • Methylprednisolone clearance
  • Steroid pharmacodynamics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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