ALTERED PATTERNS OF DRUG-METABOLISM IN PATIENTS WITH ACQUIRED-IMMUNODEFICIENCY-SYNDROME

Caffeine was used to assess acetylation status and indexes of oxidative drug metabolism (demethylation, xanthine oxidation, and 8-hydroxylation) in a control group and in three groups of patients infected with human immunodeficiency virus (HIV): patients with acquired immunodeficiency syndrome (AIDS) who had acute illnesses, stable patients with AIDS, and asymptomatic patients infected with HIV. The prevalence of apparent slow acetylation was greater in AIDS patients with acute illnesses compared with control subjects (27 of 29 [93%] versus 18 of 29 [62%]). Indexes of demethylation were decreased and 8-hydroxylation increased in these patients. Xanthine oxidation was the same as that in the control subjects. In the stable AIDS patients, oxidative pathways were altered in a manner similar to that observed in the AIDS patients with acute illnesses, but acetylation was the same as that in the control subjects. In HIV-infected asymptomatic patients, drug metabolism was the same as that in the control subjects. The increased prevalence of apparent slow acetylation and the altered activity of the oxidative pathways in AIDS patients with acute illnesses may partly explain the increased incidence of adverse drug reactions in these patients.