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); N-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.
Lee
B L
BL
Department of Medicine, University of California, San Francisco.
Delahunty
T
T
Safrin
S
S
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000652:urine*; D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000652:urine*; D013420:Sulfamethoxazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
C059873:sulfamethoxazole hydroxylamine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013420:Sulfamethoxazole; D002955:Leucovorin