Oral absorption of trimethoprim-sulfamethoxazole in patients with AIDS

Abstract

Study objective: To determine the bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) in patients infected with the human immunodeficiency virus (HIV).

Design: Open-label, randomized, two-way crossover trial.

Setting: Outpatient clinical research center affiliated with a community-based teaching hospital.

Patients: Ten individuals diagnosed with the acquired immunodeficiency syndrome (AIDS) with CD4+ counts less than 200 cells/mm3, receiving TMP-SMX one double-strength tablet 3 times/week as prophylaxis for Pneumocystis carinii pneumonia (PCP), and without documented gastroenteropathy or diarrhea agreed to participate in the trial. One patient withdrew from the study secondary to development of symptomatic PCP. Data were available for analysis from the remaining nine subjects.

Interventions: Participants received TMP 160 mg and SMX 800 mg orally or intravenously during two study periods. Following dose administration, blood samples were collected at predetermined time points over 36 hours.

Measurements and main results: Analysis of TMP-SMX pharmacokinetic parameters (half-life, total body clearance, area under the serum concentration versus time curve, and peak concentration) failed to reveal any significant differences between intravenous and oral preparations. The calculated bioavailabilities of oral TMP and SMX (mean +/- SD) were 102.7% +/- 19.8% and 109.4% +/- 19.4%, respectively.

Conclusion: The absorption of TMP-SMX is not adversely affected by HIV infection in the absence of HIV-induced gastroenteropathy or diarrhea.