Effect of Omeprazole and Dextromethorphan on the Urinary Metabolic Ratio of Flurbiprofen.

Interindividual differences in drug response - especially due to drug metabolism - are among the most important reasons for severe adverse drug reactions (ADR) in patients. About 80% of drugs causing clinically relevant ADR are metabolized by polymorphic enzymes [1]. The most important human enzymes for oxidative drug metabolism belong to the cytochrome P450 (CYP) monooxygenase superfamily. Several CYP possess high levels of genetic polymorphism and can be induced or inhibited, thereby causing pronounced interindividual differences in enzyme activity and drug response. The assessment of CYP activity (phenotyping) of a patient before drug treatment might minimize the occurrence of ADR and treatment failures. In the last decades, CYP phenotyping procedures were simplified by combining up to five probe drugs into a so-called probe drug cocktail [2-8]. Two of these, the Pittsburgh and the Geneva cocktail, use flurbiprofen (FLB) as CYP2C9 probe drug [8-10]. It was recently shown that the metabolic ratio of FLB measured in plasma 2 hr after administration was not influenced by a combination of flurbiprofen with caffeine, omeprazole, dextromethorphan and midazolam [9]. As urine can also be used for CYP2C9 phenotyping [3], we aimed to verify whether the urinary measure is also unaffected by concomitant administration of the probe drugs dextromethorphan (CYP2D6) or omeprazole (CYP2C19).