The effect of cimetidine on the formation of sulfamethoxazole hydroxylamine in patients with human immunodeficiency virus.
Hypersensitivity reactions from trimethoprim/sulfamethoxazole are likely caused by a reactive nitroso intermediate formed from sulfamethoxazole hydroxylamine. This pilot study tested whether cimetidine inhibits the urinary excretion of sulfamethoxazole hydroxylamine. Ten outpatients infected with human immunodeficiency virus (HIV) and currently receiving trimethoprim/sulfamethoxazole prophylaxis were randomly selected from 59 eligible patients. Five received cimetidine 800 mg twice daily for 1 week and five served as controls. Two spot urine samples one week apart were obtained after a trimethoprim/sulfamethoxazole dose for all patients. Patients taking cimetidine had a significant decrease in excretion of sulfamethoxazole hydroxylamine relative to total excreted drug in the two urine samples compared with control patients. Cimetidine likely caused this decrease in sulfamethoxazole hydroxylamine excretion through inhibition of CYP3A4. Because of potential differences between HIV-infected patients and healthy subjects in oxidative metabolism, future studies of inhibitors of sulfamethoxazole hydroxylamine formation should be conducted in the HIV population.
Lehmann
D F
DF
Department of Medicine, School of Medicine, State University of New York Health Science Center at Syracuse 13210, USA.
Newman
N
N
Morse
P D
PD
D000328:Adult; D000890:Anti-Infective Agents / Q000378:metabolism / Q000652:urine; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019072:Antibiotic Prophylaxis; D002927:Cimetidine / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000378:metabolism* / Q000652:urine; D006801:Humans; D008297:Male; D010865:Pilot Projects; D013420:Sulfamethoxazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D014295:Trimethoprim / Q000378:metabolism / Q000652:urine
D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; C059873:sulfamethoxazole hydroxylamine; D002927:Cimetidine; D014295:Trimethoprim; D013420:Sulfamethoxazole