title: Hemolytic and pharmacokinetic studies of liposomal and particulate amphotericin B formulations.
abstract: Amphotericin B (AmB) is a very effective antifungal and antiparasitic drug with a narrow therapeutic window. To improve its efficacy/toxicity balance, new controlled release formulations have been developed based on different encapsulation systems, aggregation states and particle sizes modifications. The kinetics of the hemolytic process was studied not only to characterize the toxicity of different formulations but also as an indicator of drug release. Pharmacokinetic studies in beagle dogs were carried out with those formulations that exhibited the least hemolytic toxicity: liposomal formulation (AmBisome), poly-aggregated AmB and encapsulated particulate AmB formulation. A novel poly-aggregated AmB formulation proved to be comparable in terms of low hemolytic activity with the marketed gold standard formulation: AmBisome. Its pharmacokinetic profile, characterized by a smaller area under the curve and larger volume of distribution, was markedly different from AmBisome, resulting in a cost-effective alternative for the treatment of leishmaniasis which can enhance the AmB passive target by the uptake by the cells of the reticulo-endothelial system. Effects of different variables such as type of formulation, dose, microencapsulation, anesthesia and dog's healthy state on AmB pharmacokinetics were studied.
authors: Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramon y Cajal, 28040 Madrid, Spain.
authors: Dolores R
authors: DR
authors: Serrano
authors: Leticia
authors: L
authors: Hernández
authors: Laura
authors: L
authors: Fleire
authors: Iban
authors: I
authors: González-Alvarez
authors: Ana
authors: A
authors: Montoya
authors: María P
authors: MP
authors: Ballesteros
authors: María A
authors: MA
authors: Dea-Ayuela
authors: Guadalupe
authors: G
authors: Miró
authors: Francisco
authors: F
authors: Bolás-Fernández
authors: Juan J
authors: JJ
authors: Torrado
mesh_terms: D061605:Administration, Intravenous; D000666:Amphotericin B / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004283:Dog Diseases / Q000378:metabolism; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007896:Leishmaniasis / Q000378:metabolism / Q000662:veterinary; D008297:Male; D010316:Particle Size
chemical_list: D000935:Antifungal Agents; D000981:Antiprotozoal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B