Urinary recovery and kinetics of sulphamethoxazole and its metabolites in HIV-seropositive patients and healthy volunteers after a single oral dose of sulphamethoxazole.
1. The urinary excretion of sulphamethoxazole and its metabolites was compared between healthy volunteers and HIV-seropositive patients in order to get a better understanding of why HIV seropositives are more predisposed to idiosyncratic toxicity of sulphonamides. 2. A single 800 mg oral dose of sulphamethoxazole was administered to seven healthy volunteers and seven asymptomatic HIV seropositives without previous use of sulphonamides. 3. Urine was collected for 4 days and drug analysis was by h.p.l.c. 4. No difference was observed between seropositive and seronegative individuals in the urinary recovery of sulphamethoxazole, N4-acetyl-, 5-hydroxy-, N4-acetyl-5-hydroxy-sulphamethoxazole and the N1-glucuronide conjugate. However the recovery of the hydroxylamine metabolite of sulphamethoxazole was significantly lower in the HIV seropositives (0.50 +/- 0.51 vs 2.23 +/- 0.85%; 95% CI on the difference, -0.90 to -2.55; P = 0.0006). 5. Sulphamethoxazole hydroxylamine may be a factor in the susceptibility of HIV infected individuals to sulphonamides.
van der Ven
A J
AJ
Department of General Internal Medicine, Academic Hospital, Nijmegen St Radboud, The Netherlands.
Vree
T B
TB
van Ewijk-Beneken Kolmer
E W
EW
Koopmans
P P
PP
van der Meer
J W
JW
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D013420:Sulfamethoxazole