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

Abstract

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.

• Authors: B L Lee, T Delahunty, S Safrin
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 56 Issue 2 Pg. 184-9 (Aug 1994) ISSN: 0009-9236 [Print] United States
• PMID: 8062495 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• sulfamethoxazole hydroxylamine
• Trimethoprim, Sulfamethoxazole Drug Combination
• Sulfamethoxazole
• Leucovorin

Topics

• AIDS-Related Opportunistic Infections (drug therapy, urine)
• Administration, Oral
• Adult
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Injections, Intravenous
• Leucovorin (therapeutic use)
• Male
• Middle Aged
• Pneumonia, Pneumocystis (drug therapy, urine)
• Sulfamethoxazole (analogs & derivatives, metabolism, urine)
• Trimethoprim, Sulfamethoxazole Drug Combination (administration & dosage, adverse effects, therapeutic use)