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M9490651.TXT
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1994-09-24
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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
protected by Copyright Law (Title 17, U.S.Code).