Dapsone, Trimethoprim, and Sulfamethoxazole Plasma Levels during Treatment of Pneumocystis Pneumonia in Patients with the Acquired Immunodeficiency Syndrome (AIDS)

Evidence of Drug Interactions

  1. Belle L. Lee, PharmD;
  2. Medina Ileana, MD;
  3. Neal L. Benowitz, MD;
  4. Jacob Peyton III, PhD;
  5. Constance B. Wofsy, MD; and
  6. Mills V John, MD

    Abstract

    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.

    Article and Author Information

    • From San Francisco General Hospital Medical Center and the University of California, San Francisco; San Francisco, California. For current author addresses, see end of text.

    • Grant Support: Partial support by grant FDR-000137-01-1 from the U.S. Food and Drug Administration, grant 2-534996-19900 from the State of California Universitywide Task Force on AIDS, and by the AIDS Clinical Study Center of the University of California, San Francisco. Dr. Lee was supported by training grant GM-07546 from the National Institutes of Health.

    • Requests for Reprints: Belle L. Lee, PharmD, San Francisco General Hospital Medical Center, 1001 Potrero Avenue, Room 5H22, San Francisco, CA 94110.

    • Current Author Addresses: Drs. Lee, Benowitz, Jacob, Wofsy, and Mills: San Francisco General Hospital, San Francisco, CA 94110.

      Dr. Medina: Department of Medicine, Highland Hospital, Oakland, CA 94602.

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    1. Ann Intern Med April 15, 1989 vol. 110 no. 8 606-611
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