A Phase I Study of the Safety, Tolerance, and Study of the Pharmacokinetics of Aerosolized Pentamidine and Parenteral Pentamidine in Children With HIV Infection and Suspected Pneumocystis Carinii Pneumonia

Pneumocystis carinii pneumonia (PCP) is the most common serious infection in children with AIDS and is associated with a high death rate. Current approved treatment includes intravenous trimethoprim - sulfamethoxazole (TMP / SMX) and intravenous pentamidine, which are both effective in treatment of the first episode of PCP pneumonia. However, both therapies have a 50 percent or greater incidence of adverse reactions. Because of serious toxicities, drug treatment has had to be discontinued. Animal studies show that aerosolized pentamidine (pentamidine given through inhalation) is as effective as intravenous pentamidine. It is hoped that the aerosolized route will be less toxic than intravenous pentamidine. The study is the first step in evaluating the delivery of aerosolized pentamidine to children.

Sixteen patients are assigned into one of the following groups. Group 1 (four patients) receives intravenous pentamidine as a one-time dose, infused over 2 hours. Group 2a (six patients) receives aerosolized pentamidine via face mask. Group 2b (six patients) receives aerosolized pentamidine 2 times. Group 2b will be studied only if initial dose is well tolerated. Small amounts (1 - 2 cubic centimeters) of blood is taken from all groups at 40 minutes, and 2, 3, 7, 14, and 24 hours from the beginning of pentamidine treatment and at the same time as the lung biopsy or bronchial alveolar lavage. Patients are given routine TMP / SMX (or whatever medications are considered appropriate by the patient's primary physician for medical management) dosing 1 - 2 hours after pentamidine is given. Bronchial alveolar lavage fluid or lung tissue from biopsy will be obtained between 2 - 48 hours after initiation of pentamidine treatment (optionally 10 - 24 hours post dose).