Functional phenotyping of the CYP2D6 probe drug codeine in the horse

Abstract Background In humans, the drug metabolizing enzyme CYP2D6 is highly polymorphic resulting in substantial differences metabolism of drugs including anti-arrhythmics, neuroleptics, and opioids. The objective this study was to phenotype a population 100 horses from five different breeds assess metabolic activity equine homolog using codeine as probe drug. Administration common method used for patient phenotyping human medicine, whereby ratio parent metabolite (metabolic ratio, MR) can be compare relative function between individuals. A single oral dose (0.6 mg/kg) administered plasma concentrations its metabolites were determined liquid chromatography mass spectrometry. MR O-demethylation [(codeine)/(morphine + morphine-3-glucuronide morphine-6-glucuronide)] area under concentration-time curve extrapolated time zero infinity (AUC 0-∞ ) each analyte group into predicted phenotypes (high-, moderate-, low-MR). Results ranged 0.002 0.147 (median 0.018) among all horses. No significant difference observed breeds, age, or sex. Of horses, 11 classified high-MR, 72 moderate-MR, 17 low-MR. Codeine AUC significantly ( p < 0.05) three groups. mean ± SD 0.089 0.027, 0.022 0.011, 0.0095 0.001 high-, low-MR groups, respectively. morphine morphine-6-glucuronide high-and groups 0.004 0.006). Conclusions calculated following administration allowed classification within large population. range suggests presence genetic polymorphisms CYP2D82 which known substrate. Additional studies genotyping high- individuals are necessary determine CYP2D their functional implications with respect therapeutics.