S-MEPHENYTOIN HYDROXYLATION POLYMORPHISM AND ITS RELATION TO DEBRISOQUINE HYDROXYLATION PHENOTYPE IN NATIVE NORMAL CHINESE SUBJECTS

Mephenytoin (100mg) and debrisoquine (10mg) were coadministered orally. Theratio between the S- and R- enantiomers of mephenytoin and the ration between debrisoquine and 4- hydroxyldebrisouine (metabolic ratio, MR) in 8 h urine were determined by gas chromatography withNPD or PID respectively. These ratios were used as measures of drug hydroxylation capacity. In the137 native normal Chinese subjects the frequency of PMs of s-mephenytoin hydroxylation was foundto be 14.6% (20/137) which is similar to the previously reported results in Japanese population (18-22%), but much higher than that in the Caucasian populations (2.4-5.4%). Thus, we can concludethat there are pronounced differences in the incidence of S-mephenytoin hydroxylation of PMs betweenOriental and Caucasian populations. Our results also showed that there was no relationship between S-mephenytoin and debrisoquine hydroxylation phenotypes in 137 native Chinese subjects. These dis-parate findings demonstrated that the S-mephenytoin and debrisoquine hydroxylases are two differentisozymes of the cytochrome P_(450) family and the independence of two oxidative metabolizing traits.