Study Objective: To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS).
Design: Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS.
Setting: County hospital and AIDS clinic.
Patients: Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole.
Intervention: Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg · d; administered for 21 days.
Measurements and Main Results: Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 µg/mL; P < 0.05). Trimethoprim-dapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 µg/mL; P < 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%).
Conclusions: A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.