Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations

Abstract

Interethnic differences in debrisoquin and mephenytoin hydroxylation have been compared between normal white (n = 183) and Japanese (n = 100) subjects with the 8-hour urinary metabolic ratio of debrisoquin and the urinary S/R enantiomeric ratio of mephenytoin to identify extensive (EM) and poor (PM) metabolizers. In white subjects the frequency of PMs was 8.7% and 2.7% for debrisoquin and mephenytoin, respectively. In contrast, in Japanese subjects no PMs of debrisoquin were identified, while the incidence of PMs of mephenytoin was 18%. These substantial differences (P less than 0.001) in polymorphic distributions of oxidative drug metabolizing ability have implications for interethnic efficacy and toxicity of drugs and other xenobiotics that are metabolized by the involved cytochrome P-450 isozymes.

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

“…Tamminga et al have also describes an effect of OCs using S-mephynotoin as a probe drug [26]. The oral contraceptives may contain progestin with or without ethinyl oestradiol and it is not known whether it is the oestrogen or the progestin component that inhibits drug metabolism [10]. The inhibition of CYP2C19 activity by OC seems to be due to the ethinyloestradiol component of OCs [27,28].…”

“…About 3 % of Caucasians are PM of S-mephenytoin [8 , 9] and a higher incidence of PMs has been reported in Japanese (18-23 %) [10,11] Chinese (15-17%) [12,13] and in Korean subjects (13-16%) [14]. The PM phenotype is caused by the CYP2C19*2 [15] and CYP2C19*3 alleles although the CYP2C19*3 is very uncommon in Caucasian PMs [16].…”

Uses and misuses of definitions of genetic polymorphism. A perspective from population pharmacogenetics [letter]

“…Inversely, if the number of poor metabolizers is below 1-2%, polymorphism is said not to be evident or its absence could have been implied (Arias et al, 1986; Correspondence: Professor T. D. Arias, Apartado 10767, Estafeta Universitaria, Panama, Republica de Panama. Iyun et al, 1986;Lou et al, 1987;Nakamura et al, 1985;Tucker et al, 1986;Woolhouse et al, 1985). This view is shared by all researchers in population pharmacogenetics who have claimed absence of evidence for the existence of polymorphism, and, presumably, by the editors and most of the reviewers of their publications.…”

Validated ion pair liquid chromatography/fluorescence detection method for assessing the variability of the loratadine metabolism occurring in bioequivalence studies

“…Reported pharmacokinetic parameters for LOR and DCL obtained after the administration of 20 mg of LOR to Caucasian volunteers have shown a significant variability (Hilbert et al, 1987;Sutherland et al, 2001). This variability is related to genetic polymorphism, as 7-10% of Caucasian individuals posses CYP2D6 expression related to a poor metabolization phenotype (Alvan et al, 1990;Nakamura et al, 1985).…”