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Influence of double genetic polymorphism on response to sulfamethazine
Author(s) -
Woolhouse N M,
AtuTaylor L C
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.48
Subject(s) - hemolysis , glutathione , chemistry , pharmacology , glucose 6 phosphate dehydrogenase , plasma concentration , drug , medicine , dehydrogenase , biochemistry , enzyme
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 concentrations 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 were 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. Clinical Pharmacology and Therapeutics (1982) 31, 377–383; doi: 10.1038/clpt.1982.48