Biocompatible microemulsion modifies the pharmacokinetic profile and cardiotoxicity of doxorubicin
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2013-01-01
Autores
Assumpção, Juliana Uruguay Correa Vidigal [UNESP]
Campos, Michel Leandro [UNESP]
Ferraz Nogueira Filho, Marco Antonio [UNESP]
Pestana, Kelly Chrystina [UNESP]
Baldan, Helen Mariana [UNESP]
Formariz Pilon, Thalita Pedroni
Oliveira, Anselmo Gomes de [UNESP]
Peccinini, Rosangela Goncalves [UNESP]
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Resumo
Doxorubicin (DOX) is an anthracycline antibiotic with a broad antitumor spectrum. However, the clinical use of DOX is limited because of its cardiotoxicity, a dose-dependent effect. Colloidal drug delivery systems, such as microemulsions (MEs), allow the incorporation of drugs, modifying the pharmacokinetic (PK) profile and toxic effects. In this study, we evaluated the PK profile and cardiotoxicity of a new DOX ME (DOX-ME). The PK profile of DOX-ME was determined and compared with that of the conventional DOX after single-dose administration (6mg/kg, intravenous) in male Wistar rats (n = 12 per group). The cardiotoxicity of DOX formulations was evaluated by serum creatine kinase MB (CKMB) activity in both animal groups before and after drug administration. The plasma DOX measurements were performed by high-performance liquid chromatography with fluorescence detection, and the CKMB levels were assayed using the CKMB Labtest® kit. The ME system showed a significant increase in plasma DOX concentrations and lower distribution volume when compared with conventional DOX. Serum CKMB activity increased after conventional DOX administration but was unchanged in the DOX-ME group. These results demonstrate modifications in drug access to susceptible sites using DOX-ME. DOX-ME displayed features that make it a promising system for future therapeutic application. © 2012 Wiley Periodicals, Inc.
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Biocompatible microemulsion, Cancer chemotherapy, Cardiotoxicity, CKMB, Distribution, Doxorubicin, HPLC (High-Performance/Pressure-Liquid-Chromatography), Pharmacokinetics, Toxicology, creatine kinase MB, doxorubicin, animal experiment, animal model, biocompatibility, blood sampling, cardiotoxicity, drug blood level, drug formulation, enzyme activity, fluorescence analysis, high performance liquid chromatography, male, microemulsion, nonhuman, rat, single drug dose, Animals, Antibiotics, Antineoplastic, Biological Markers, Chemistry, Pharmaceutical, Chromatography, High Pressure Liquid, Creatine Kinase, MB Form, Emulsions, Heart Diseases, Injections, Intravenous, Lipids, Male, Rats, Rats, Wistar, Technology, Pharmaceutical
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Journal of Pharmaceutical Sciences, v. 102, n. 1, p. 289-296, 2013.