Status of Aerosolized Pentamidine for Treatment and Prophylaxis of Pneumocystis carinii Pneumonia

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Abstract
Aerosolization of pentamidine is a promising novel treatment and prophylactic agent for Pneumocystis carinii pneumonia. Before aerosolization can be accepted as standard therapy, issues of targeting, pharmacokinetics, delivery systems, efficacy compared to standard therapies, and safety must be answered. Two factors favor a 1-2 micron MMAD aerosol as ideal, the first is high alveolar deposition, the second is low airway deposition, the former because the alveolus is the habitat of P. carinii, the latter because pentamidine isethionate is an airway irritant. Pharmacokinetic studies of aerosolized pentamidine in both animals and human with aerosols in this size range have documented a long alveolar half life and high alveolar levels in patients or animals with or without acute P. carinii pneumonia. Current nebulizers are limited by either poor efficiency or large particles that increase the incidence of cough or bronchospasm. Pilot studies of aerosolized pentamidine for treatment of P. carinii pneumonia have reported conflicting results which may be from methods of administration. Prophylaxis of P. carinii pneumonia with aerosolized pentamidine is effective at 300 mg once a month dose using a Respiragrd II nebulizer. Aerosolized pentamidine appears safe, common side effects are cough and bronchospasm. Both can be ameliorated or prevented by aerosolized bronchodilators.