ABNORMALITIES IN THE METABOLISM OF ACETAMINOPHEN IN PATIENTS INFECTEDWITH THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)

The urinary concentration of acetaminophen and its glucuronide, sulpha te, cysteine, and mercapturate conjugates was measured by high-perform ance liquid chromatography in 32 healthy volunteers, 9 untreated sympt om-free HIV-seropositive subjects, and 19 patients with AIDS after a s ingle oral dose of 1.5 g of acetaminophen The concentration of the glu curonide conjugate was significantly lower in AIDS patients when simul taneously compared with concentrations found in healthy individuals an d symptom-free HIV-seropositive subjects. Differences between healthy volunteers and symptom-free HIV seropositives were not encountered. By contrast, urinary concentrations of sulphate and oxidation pathway-de rived metabolites were significantly higher in AIDS patients as compar ed with the other two groups. When AIDS patients treated with zidovudi ne were compared with those not given this medication, differences in the urinary excretion of acetaminophen and its metabolites were not ob served. However, the urinary concentration of mercapturic acid was sig nificantly higher in those given enzyme inducers, such as rifampicin o r phenytoin, than in AIDS patients not treated with these drugs. In su mmary, patients with advanced HIV infection showed reduced acetaminoph en glucuronidation and increased formation of the hepatotoxic oxidatio n metabolites, which was independent of zidovudine therapy.