INTERETHNIC DIFFERENCES IN DRUG-METABOLISM - INFLUENCE OF GENETIC ANDENVIRONMENTAL-FACTORS ON DEBRISOQUINE HYDROXYLATION PHENOTYPE

Genetic and environmental factors are determinants of the interindivid ual and interethnic variability in drug metabolism. The metabolism of several important drugs (e.g. haloperidol) cosegregates with that of d ebrisoquine. Thus, interethnic differences in debrisoquine hydroxylati on polymorphism (CYP2D6) might be partly responsible for the variation s in haloperidol disposition between races. The influence of tobacco, ethanol, caffeine, gender, and oral contraceptive use on the debrisoqu ine metabolic ratio (MR) has been analyzed in 633 Spanish healthy volu nteers. MR was also determined in panels of healthy volunteers. 18 smo kers were studied during a tobacco abstinence period, and 31 women thr ee times during the same menstrual cycle. Among EMs, debrisoquine MR w as significantly (P < 0.05) lower during smoking cessation (mean antil og +/- SD, 0.48 +/- 0.29) compared to a smoking period (0.61 +/- 0.23) . During the lutheal phase of the menstrual cycle, debrisoquine MR was also significantly (P < 0.01) lower (0.33 +/- 0.41) compared to the o vulatory-phase (0.41 +/- 0.34) and the phase before ovulation (0.44 +/ - 0.36). Among EMs, it is suggested that debrisoquine MR may be modifi ed by tobacco smoking and sexual hormones. The clinical relevance of t hese findings remains unclear.