Amphotericin B and pulmonary surfactant.
Targeted intrapulmonary delivery of drugs may reduce systemic toxicity, improve treatment efficacy, but inhaled drugs may also interfere with pulmonary surfactant function. We hypothesized that the lipophilic drug amphotericin B used to treat or prevent pulmonary infections with aspergillus species, might destroy surface activity of lung surfactant, as assessed in a pulsating bubble surfactometer. Pure amphotericin B had no effect on a natural surfactant preparation or on the lipid extracted surfactant SurvantaTM. However, amphotericin BTM (containing deoxycholic acid) or deoxycholic acid alone inhibited surfactant surface activity dose dependently and perturbed lipid organization. AmbisomeTM containing amphotericin B associated with liposomes, only marginally affected surfactant function. Intrapulmonary delivery of large amounts of amphotericin BTM has to consider the potential of interferences with lung surfactant function.
The Lung Research Group, Kinderpoliklinik, Ludwig-Maximilians-University, Pettenkoferstr 8a, D-80336 Munich, Germany. griese@pk-i.med.uni-muenchen.de
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D000280:Administration, Inhalation; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001228:Aspergillosis / Q000188:drug therapy / Q000378:metabolism; D001688:Biological Products; D002417:Cattle; D003840:Deoxycholic Acid / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013500:Surface Tension
D000935:Antifungal Agents; D001688:Biological Products; D008081:Liposomes; D011663:Pulmonary Surfactants; D003840:Deoxycholic Acid; D000666:Amphotericin B; C072197:beractant