Abnormalities in the metabolism of acetaminophen in patients infected with the human immunodeficiency virus (HIV).
The urinary concentration of acetaminophen and its glucuronide, sulphate, cysteine, and mercapturate conjugates was measured by high-performance liquid chromatography in 32 healthy volunteers, 9 untreated symptom-free HIV-seropositive subjects, and 19 patients with AIDS after a single oral dose of 1.5 g of acetaminophen. The concentration of the glucuronide conjugate was significantly lower in AIDS patients when simultaneously compared with concentrations found in healthy individuals and symptoms-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-derived metabolites were significantly higher in AIDS patients as compared with the other two groups. When AIDS patients treated with zidovudine were compared with those not given this medication, differences in the urinary excretion of acetaminophen and its metabolites were not observed. However, the urinary concentration of mercapturic acid was significantly higher in those given enzyme inducers, such as rifampicin or phenytoin, than in AIDS patients not treated with these drugs. In summary, patients with advanced HIV infection showed reduced acetaminophen glucuronidation and increased formation of the hepatotoxic oxidation metabolites, which was independent of zidovudine therapy.
Esteban
A
A
Hospital General Universitario de Elche, Spain.
Pérez-Mateo
M
M
Boix
V
V
González
M
M
Portilla
J
J
Mora
A
A
D000082:Acetaminophen / Q000378:metabolism* / Q000652:urine; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000378:metabolism* / Q000652:urine; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D008297:Male; D012016:Reference Values; D015215:Zidovudine / Q000627:therapeutic use
D018712:Analgesics, Non-Narcotic; D000998:Antiviral Agents; D000082:Acetaminophen; D015215:Zidovudine