title: Pharmacogenetic interactions in G6PD deficiency and development of an in vitro test to predict a drug's hemolytic potential.
abstract: To summarize our results and their implications, by adding induced mouse liver microsomes to an in vitro test for the hemolytic potential of a drug in G6PD deficiency, we found that: 1) Hydroxylation appears to play an important role in activating the hemolytic potential of many drugs. 2) Use of an in vitro test system combining drug, hydroxylation system and red cell, appears to be very reliable in ruling out hemolytic potential, when it is in fact absent, and about 80% effective in identifying hemolytic potential when it is present. 3) Acetylation seems to markedly reduce the hemolytic potential of two drugs studied: promizole and DDS. The genetic polymorphism in acetylation may explain the bimodal response to promizole. 4) These studies suggest that interaction among three pharmacogenetic systems produces a given hemolytic result. Variability of hydroxylation and acetylation rates can be expected to contribute to variability in individual responses to certain hemolytic drugs.
mesh_terms: D000818:Animals; D003622:Dapsone / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood*; D005978:Glutathione / Q000097:blood*; D006461:Hemolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D013450:Sulfones; D013844:Thiazoles; D003622:Dapsone; D005978:Glutathione; C009453:thiazosulfone