Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection.
prospective_cohort · Level II
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Abstract
BACKGROUND: Reports suggest that antituberculosis drugs are malabsorbed in patients with advanced HIV disease. OBJECTIVE: To evaluate the pharmacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease. DESIGN: Parallel study. SETTING: Two hospital outpatient clinics. PARTICIPANTS: 12 healthy volunteers, 12 patients with asymptomatic HIV disease, 12 patients with symptomatic HIV disease, and 12 patients with symptomatic HIV disease and diarrhea. MEASUREMENTS: Drug plasma concentrations were measured over 24 hours on day 4 of concurrent therapy. INTERVENTION: Oral isoniazid (300 mg/d), rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d). RESULTS: Reduced total drug exposure to rifampin and pyrazinamide was associated with D-xylose malabsorption in persons with HIV infection or AIDS. Peak drug exposure to isoniazid was lower in patients with diarrhea. CONCLUSIONS: Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.