The hydroxylamine of sulfamethoxazole and adverse reactions in patients with acquired immunodeficiency syndrome

We measured the urine concentrations of sulfamethoxazole, sulfamethoxazole hydroxylamine, and N‐ sulfamethoxazole on days 3 and 10 in 15 patients with acquired immunodeficiency syndrome treated with a combination product of trimethoprim (15 mg/kg/day) and sulfamethoxazole (75 mg/kg/day). The percentage of sulfamethoxazole and metabolites excreted on days 3 and 10, respectively, were sulfamethoxazole 17.2% ± 11.3% versus 15.6% ± 8.2%; sulfamethoxazole hydroxylamine 2.6% ± 2.0% versus 5.0% ± 5.2% ( p < 0.05); AT‐acetylsulfamethoxazole 80.0% ± 12.9% versus 79.8% ± 11.8%. The percentage of sulfamethoxazole hydroxylamine excreted was similar between the eight patients who discontinued therapy because of toxicity and the seven patients who did not (2.9% ± 2.3% versus 2.3% ± 2.0%, p = 0.7). In two patients who had major liver toxicity the percentage of sulfamethoxazole hydroxylamine excreted was significantly lower than that of the 13 patients who did not (0.8% ± 0.1% versus 2.9% ± 2.0%, p < 0.05). This is the first report of the formation and excretion of sulfamethoxazole hydroxylamine in patients with acquired immunodeficiency syndrome. With 15 patients we were unable to show a significant correlation between the percentage of sulfamethoxazole hydroxylamine excreted and adverse reactions. However, patients with liver toxicity excreted less sulfamethoxazole hydroxylamine. Clinical Pharmacology and Therapeutics (1994) 56, 184–189; doi: 10.1038/clpt.1994.122