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Intravenous or Inhaled Pentamidine for Treating Pneumocystis carinii Pneumonia in AIDS: A Randomized Trial

John E. Conte Jr., MD; David Chernoff, MD; David W. Feigal Jr., MD, MPH; Pat Joseph, MD; Charles McDonald, MD; and Jeffrey A. Golden, MD
[+] Article, Author, and Disclosure Information

Grant Support: In part by the Division of Research Resources, R79, U.S. Public Health Service; the University wide Task Force on AIDS Award (R87SF087); and Lypho Med, Inc.

Requests for Reprints: John E. Conte, Jr., MD, Department of Medicine, Medical Center at the University of California, 505 Parnassus Avenue, San Francisco, CA 94143-0208.

Current Author Addresses: Drs. Conte, Chernoff, and Golden: Department of Medicine, Medical Center at the University of California, San Francisco, CA 94143-0208.

Dr. Feigal: UCSD Medical Center, San Diego, CA 92103.

Dr. Joseph: Adult Immunology and AIDS Clinic, Peralta Hospital, Hawthorne Avenue and Webster Street, Oakland, CA 94609.

Dr. McDonald: Pacific Presbyterian Medical Center, 2333 Buchanan, San Francisco, CA 94115

© 1990 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1990;113(3):203-209. doi:10.7326/0003-4819-113-3-203
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Objective: To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS).

Design: Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid.

Patients: Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (PaO2 ≥ 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine.

Interventions: Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks.

Measurements and Main Results: The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], -23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (±SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 ± 65.1 ng/mL compared with 14.4 ± 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 ± 16.4, 56.5 ± 26.1, and 61.1 ± 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively.

Conclusions: The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.





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