METABOLIC RATIOS OF 4 PROBES OF CYP2D6 IN TURKISH SUBJECTS - A CROSS-OVER STUDY

The relationships among the metabolic ratios for the standard probe dr ugs of CYP2D6 activity, such as debrisoquine, sparteine, metoprolol. a nd 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 debris oquine previously. All subjects were given a 10 mg debrisoquine tablet , a 100 mg sparteine tablet, a 100 mg.metoprolol tablet and a 20 mg de xtromethorphan capsule orally with a wash-out period of at least 1 wee k between each probe administration. Metabolic ratios were calculated as percentage of dose excreted as parent drug/percentage of dose excre ted 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 phenotypin g methods was observed. All six correlations among the metabolic ratio s of the 4 probe drugs assessed by Spearman's rank test were highly si gnificant (P < 0.001). The present findings indicate that the oxidativ e metabolism of debrisoquine, sparteine, metoprolol and dextromethorph an is catalysed by the same cytochrome P450 in the Turkish subjects.