Metabolic ratios of four probes of CYP2D6 in Turkish subjects: A cross-over study

The relationships among the metabolic ratios for the standard probe drugs of CYP2D6 activity, such as debrisoquine, sparteine, metoprolol. and dextromethorphan, were studied in 32 Turkish subjects. All subjects were randomly selected according to their phenotypes from a group of 111 Turkish subjects whose oxidation status had been tested for debrisoquine previously. All subjects were given a 10 mg debrisoquine tablet, a 100 mg sparteine tablet, a 100 mg.metoprolol tablet and a 20 mg dextromethorphan capsule orally with a wash-out period of at least 1 week between each probe administration. Metabolic ratios were calculated as percentage of dose excreted as parent drug/percentage of dose excreted as its hydroxymetabolite of parent drug in 0-8 h urine. Three poor metabolisers (PM) of debrisoquine were identified. They were also PMs of the other test probes and no misclassification by the 4 phenotyping methods was observed. All six correlations among the metabolic ratios of the 4 probe drugs assessed by Spearman's rank test were highly significant (P < 0.001). The present findings indicate that the oxidative metabolism of debrisoquine, sparteine, metoprolol and dextromethorphan is catalysed by the same cytochrome P450 in the Turkish subjects.