B. Ozkartal; T. Bakirel
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Istanbul University, Istanbul, Turkey
Amphotericin B (AmB) has been the most effective systemic antifungal agent. Despite its proven clinical efficacy, its use has been limited by the narrow therapeutic index of the conventional formulation (Fungizone). The dose-limiting toxicity of Fungizone is being addressed by new formulations that utilize either liposomes or lipid complexes as drug carriers. One of the most widely used of these new formulations is AmBisome. Despite its long history of use, much is still unknown concerning the pharmacokinetics of AmB especially in the veterinary-treated animals. To understand the therapeutic properties of liposomal amphotericin B, and evaluate potential differences between it and other AmB formulations, it is important to determine how liposomal amphotericin B alters the disposition of amphotericin B. Therefore, this study was conducted to compare the pharmacokinetic characteristics of AmBisome with Fungizone in dogs.
Dogs received a single intravenous infusion of Fungizone or AmBisome (0.6 mg/kg), and blood samples were collected until the 96th hour after dosing. The concentrations of AmB were determined using HPLC and the pharmacokinetic parameters were calculated.
From detected plasma concentrations, it is stated that both of the drugs fitted to two-compartment model. AmBisome had at least 8-fold greater Cmax than Fungizone; however, the volume of distribution of AmB appeared to be about 7-fold lower with AmBisome than with Fungizone.
The pharmacokinetics properties of AmBisome were different from those of Fungizone. AmBisome, which had higher concentration and longer residence time in plasma relative to the conventional form, would be a good candidate for an AmB formulation in dogs.