title: Influence of double genetic polymorphism on response to sulfamethazine.
abstract: Combined effects of a double genetic polymorphism on sulfamethazine-induced changes in erythrocyte-reduced glutathione (GSH) concentration were investigated in 16 healthy Ghanaian men. The subjects were divided into four subgroups on the basis of their glucose-6-phosphate dehydrogenase (G-6-PD) activity levels and acetylator phenotypes. Each received a single oral dose of sulfamethazine (1.5 gm). Erythrocyte concentration of GSH and plasma concentrations of drug were determined in samples taken at specific times after dosing. Sulfamethazine treatment induced a decrease in erythrocyte GSH concentration in all subjects. The degree of exposure to sulfamethazine was greater in slow acetylators, as evidenced by higher plasma concentrations, longer half-lifes, and greater area under the plasma concentration-time curves. The greatest decrease in GSH concentration occurred in subjects who where both G-6-PD deficient and phenotypically slow acetylators. In these subjects the effect of the double genetic defect was approximately additive. Drug-induced hemolysis is associated with a low erythrocyte GSH concentration. Our data suggest that slow acetylator status is likely to increase susceptibility to hemolysis in G-6-PD-deficient individuals exposed to potentially hemolytic arylamines.
mesh_terms: D000107:Acetylation; D004912:Erythrocytes / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood* / Q000235:genetics; D005978:Glutathione / Q000097:blood; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D013418:Sulfamethazine / Q000097:blood / Q000494:pharmacology*
chemical_list: D013418:Sulfamethazine; D005978:Glutathione