URINARY RECOVERY AND KINETICS OF SULFAMETHOXAZOLE AND ITS METABOLITESIN HIV-SEROPOSITIVE PATIENTS AND HEALTHY-VOLUNTEERS AFTER A SINGLE ORAL DOSE OF SULFAMETHOXAZOLE

1 The urinary excretion of sulphamethoxazole and its metabolites was c ompared between healthy volunteers and HIV-seropositive patients in or der to get a better understanding of why HIV seropositives are more pr edisposed to idiosyncratic toxicity of sulphonamides. 2 A single 800 m g oral dose of sulphamethoxazole was administered to seven healthy vol unteers and seven asymptomatic HIV seropositives without previous use of sulphonamides. 3 Urine was collected for 4 days and drug analysis w as by h.p.l.c. 4 No difference was observed between seropositive and s eronegative 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 me tabolite of sulphamethoxazole was significantly lower in the HIV serop ositives (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 sulphonam ides.