Document 0651
 DOCN  M9490651
 TI    The hydroxylamine of sulfamethoxazole and adverse reactions in patients
       with acquired immunodeficiency syndrome.
 DT    9411
 AU    Lee BL; Delahunty T; Safrin S; Department of Medicine, University of
       California, San Francisco.
 SO    Clin Pharmacol Ther. 1994 Aug;56(2):184-9. Unique Identifier : AIDSLINE
       MED/94340862
 AB    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.
 DE    Administration, Oral  Adult  AIDS-Related Opportunistic Infections/DRUG
       THERAPY/*URINE  Double-Blind Method  Drug Therapy, Combination  Female
       Human  Injections, Intravenous  Leucovorin/THERAPEUTIC USE  Male  Middle
       Age  Pneumonia, Pneumocystis carinii/DRUG THERAPY/*URINE
       Sulfamethoxazole/*ANALOGS & DERIVATIVES/METABOLISM/*URINE  Support, U.S.
       Gov't, P.H.S.  Trimethoprim-Sulfamethoxazole Combination/ADMINISTRATION
       & DOSAGE/  *ADVERSE EFFECTS/THERAPEUTIC USE  CLINICAL TRIAL  JOURNAL
       ARTICLE  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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