Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial.
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).


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


METHODS
Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine.


METHODS
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.


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.
Conte
J E
JE
School of Medicine, University of California, San Francisco.
Chernoff
D
D
Feigal
D W
DW
Joseph
P
P
McDonald
C
C
Golden
J A
JA
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000280:Administration, Inhalation; D000328:Adult; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010419:Pentamidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012129:Respiratory Function Tests
D010419:Pentamidine