THE EFFECT OF CIMETIDINE ON THE FORMATION OF SULFAMETHOXAZOLE HYDROXYLAMINE IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS

Hypersensitivity reactions from trimethoprim/sulfamethoxazole are like ly caused by a reactive nitroso intermediate formed from sulfamethoxaz ole hydroxylamine. This pilot study tested whether cimetidine inhibits the urinary excretion of sulfamethoxazole hydroxylamine. Ten outpatie nts infected with human immunodeficiency virus (HIV) and currently rec eiving trimethoprim/sulfamethoxazole prophylaxis were randomly selecte d from 59 eligible patients. Five received cimetidine 800 mg twice dai ly for 1 week and five served as controls. Two spot urine samples one week apart were obtained after a trimethoprim/sulfamethoxazole dose fo r all patients. Patients taking cimetidine had a significant decrease in excretion of sulfamethoxazole hydroxylamine relative to total excre ted drug in the two urine samples compared with control patients. Cime tidine likely caused this decrease in sulfamethoxazole hydroxylamine e xcretion through inhibition of CYP3A4. Because of potential difference s between HIV-infected patients and healthy subjects in oxidative meta bolism, future studies of inhibitors of sulfamethoxazole hydroxylamine formation should be conducted in the HIV population. (C) 1998 The Ame rican College of Clinical Pharmacology.