CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug

PloS One
Silvia VoglWerner K Lutz

Abstract

Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects), correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen) determined two hours after flurbiprofen (8.75 mg) administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type), and 0.113 for CYP2C9*3 (19 % of wild type). If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large...Continue Reading

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Citations

Nov 26, 2015·Expert Opinion on Drug Metabolism & Toxicology·Carolina Céspedes-GarroAdrián LLerena
Jan 19, 2016·Pharmacogenomics·Rashmi R ShahRobert L Smith
Dec 1, 2015·Basic & Clinical Pharmacology & Toxicology·Silvia VoglGilbert Schönfelder
Mar 20, 2020·Clinical Pharmacology and Therapeutics·Katherine N ThekenTilo Grosser
Oct 20, 2020·Frontiers in Pharmacology·Zahi Abu GhoshYoseph Caraco

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Datasets Mentioned

BETA
AL359672.19

Methods Mentioned

BETA
genotyping
contraception
urine collection

Software Mentioned

GraphPad Prism
SPSS
GraphPad
Analyst

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