Pneumocystis carinii Pneumonia (PCP) is an important cause of morbidity and mortality in patients with AlDS. Treatment usually requires hospitalization and is associated with significant toxicity and cost. We have recently developed a sensitive and specific HPLC assay for the measurement of pentamidine in body fluids and have reported on the pharmacokinetics of this drug in patients with normal and abnormal renal function, and on the pharmacokinetics in patients who received inhaled pentamidine. We have completed pilot studies that suggest that inhaled pentamidine is effective therapy for mild Pneumocystis carinii Pneumonia and that inhaled therapy is associated with a substantial reduction in drug toxicity. This study a) is a prospective, randomized trial which will} investigate the efficacy of two inhaled pentamidine, 300 mg(twice-monthly or 600 once-monthly, for the prevention of Pneumocysris carinii Pneumonia at risk; b) will assess the long- term toxicity of inhaled pentamidine in these patients using serial clinical and laboratory evaluations, pulmonary function testing and bronchoalveolar lavage; and c) will evaluate the plasma and bronchopulmonary pharmacokinetics of pentamidine in patients undergoing this types of prophylaxis. (One hundred and fifty patients) will be enrolled, (75) in each dose range. Outcome criteria of incidence of PCP, time to death, and toxicity will be compared for the 2 groups, and for the 2 groups versus two sets of historical controls the first is a group of 201 patients from the SFGH experience and the second is available from the UCSF AlDS registry which has 2.234 participants as of January, 1988. Peak plasma pentamidine concentrations (at the completion of inhalation) and serial laboratory tests will be performed once monthly in all patients. In a subset of ten patients, serial pulmonary function tests and repeat bronchoalveolar lavage (with lavage fluid pentamidine determinations) will be performed in order to more carefully assess long-term toxicity and bronchopulmonary pharmacokinetics.
