期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 447, 期 1-2, 页码 38-46出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.02.038
关键词
Amphotericin B; Pharmacokinetics; Hemolysis; Aggregation state; Albumin microparticles; Passive targeting
资金
- Spanish Ministry of Science and Innovation (MICINN) [AGL2007-64120/GAN]
- Complutense University
- Spanish Ministry of Education [AP2008-00235]
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 (R)), 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 (R). Its pharmacokinetic profile, characterized by a smaller area under the curve and larger volume of distribution, was markedly different from AmBisome (R), 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. (C) 2013 Elsevier B. V. All rights reserved.
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