Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs

Abstract

This study was conducted to compare the pharmacokinetic profiles of conventional (Fungizone((R))) and liposomal amphotericin B (AmBisome((R))) formulations in order to predict their therapeutic properties, and evaluate their potential differences in veterinary treatment. For this purpose, twelve healthy mixed breed dogs received both drugs at a dose of 0.6mg/kg by intravenous infusion over a 4-min period in a total volume of 40ml. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72 and 96hr after dosing, and concentrations of drug in plasma were determined by high-performance liquid chromatography (HPLC). Pharmacokinetics was described by a two-compartment model. Although both formulations were administered at the same doses (0.6mg/kg), the plasma pharmacokinetics of liposomal amphotericin B differed significantly from those of amphotericin B deoxycholate in healthy dogs (p<.05). Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14-fold higher) compared to conventional formulation. It is concluded that AmBisome((R)) reached higher plasma concentration and lower distribution volume and had a longer half-life compared to Fungizone((R)), and therefore, AmBisome((R)) is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.