title: Reduced methylprednisolone clearance causing prolonged pharmacodynamics in a healthy subject was not associated with CYP3A5*3 allele or a change in diet composition.
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.
authors.affiliation: Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: William J
authors.initials: WJ
authors.lastname: Jusko
authors.forename: Christine G
authors.initials: CG
authors.lastname: Salaita
authors.forename: Karim A
authors.initials: KA
authors.lastname: Calis
authors.forename: Michael W
authors.initials: MW
authors.lastname: Jann
authors.forename: Vicky E
authors.initials: VE
authors.lastname: Spratlin
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Goldstein
authors.forename: Yuen Yi
authors.initials: YY
authors.lastname: Hon
mesh_terms: D000328:Adult; D000483:Alleles; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004032:Diet; D006632:Histamine / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D008775:Methylprednisolone / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide
chemical_list: D006632:Histamine; D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006854:Hydrocortisone; D008775:Methylprednisolone