M. Britzi et al., Genetic polymorphism of CYP2D6 and CYP2C19 metabolism determined by phenotyping Israeli ethnic groups, THER DRUG M, 22(5), 2000, pp. 510-516
Genetic polymorphism of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 w
as determined by phenotyping four ethnic groups of the Israeli population.
The groups consisted of Ethiopian subjects, Yemenite subjects, and Russian
subjects representing first-generation new immigrants and an Israeli Arab g
roup. Dextromethorphan was used as the probe for CYP2D6 activity and mephen
ytoin was used for CYP2C19 activity. The two drugs were administered simult
aneously and urine samples were collected over a period of 8 hours. The CYP
2D6 phenotype was determined from the ratio of dextromethorphan conversion
to dextrorphan and the CYP2C19 phenotype from the ratio of S-mephenytoin an
d R-mephenytoin. The used liquid chromatographic method was able to complet
ely separate dextrorphan and dextromethorphan. Fluorescence detection allow
ed dextromethorphan quantification at 1 ng/mL. Mephenytoin enantiomers were
completely separated in high-performance liquid chromatography and the res
pective fractions were collected and analyzed using a gas chromatography/ma
ss spectrometry system with selective ion monitoring. The prevalence of poo
r metabolizer phenotype of dextromethorphan (CYP2D6) in the Yemenite (0%) a
nd Ethiopian groups (0%) was significantly different from the prevalence in
the Russian (17%) and Israeli Arab (9%) groups. A significant difference w
as also found in the distribution of the metabolic ratio of the extensive m
etabolizer phenotype between the Ethiopian group and the Russian and Yemeni
te groups. No significant difference was found in the prevalence of poor me
phenytoin metabolizer phenotype (CYP2C19) between the Yemenite (8%), Ethiop
ian (6%), Russian (9%), and Israeli Arab (8%) groups. No difference was obs
erved in the distribution of metabolic ratio within the extensive metaboliz
er phenotype subgroups of the four ethnic groups.