PROGUANIL METABOLISM IN RELATION TO S-MEPHENYTOIN OXIDATION IN A TURKISH POPULATION

The oxidation of proguanil was studied in 89 unrelated healthy Turkish volunteers after administration of proguanil (single dose, 200 mg, or ally). Based on the distribution of the ratio of proguanil to cyclogua nil excreted in urine, and using an antimode value of 15, the prevalen ce of poor metabolizers in a Turkish population was estimated to be 5. 6% (95% confidence interval 2.0%-17.3%) which was similar to that in t he other Caucasian populations. The relationship between the oxidative capacities of CYP2C19 for the two substrates, proguanil and mephenyto in, was studied in 39 subjects (two poor and 37 extensive metabolizers of proguanil). The two poor metabolizers of proguanil were also ident ified as poor metabolizers of S-mephenytoin and no misclassification b y the two phenotyping methods was observed. The correlation between th e metabolic ratio of proguanil to cycloguanil and the S/R-mephenytoin ratio as assessed by Spearman's rank test, was statistically significa nt (r(s) = 0.50, P < 0.001).