Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans.

The pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) (liposomal AMB) and the conventional formulation, AMB deoxycholate (AMB-DOC), were compared in a phase IV, open-label, parallel study in healthy volunteers. After a single 2-h infusion of 2 mg of liposomal AMB/kg of body weight or 0.6 mg of AMB-DOC/kg, plasma, urine, and feces were collected for 168 h. The concentrations of AMB were determined by liquid chromatography tandem mass spectrometry (plasma, urine, feces) or high-performance liquid chromatography (HPLC) (plasma). Infusion-related side effects similar to those reported in patients, including nausea and back pain, were observed in both groups. Both formulations had triphasic plasma profiles with long terminal half-lives (liposomal AMB, 152 ± 116 h; AMB-DOC, 127 ± 30 h), but plasma concentrations were higher (P 90% accounted for in mass balance calculations at 1 week, suggesting that metabolism plays at most a minor role in AMB elimination. In contrast, <10% of the liposomal AMB was excreted unchanged. No metabolites were observed by HPLC or mass spectrometry. In comparison to AMB-DOC, liposomal AMB produced higher plasma exposures and lower volumes of distribution and markedly decreased the excretion of unchanged drug in urine and feces. Thus, liposomal AMB significantly alters the excretion and mass balance of AMB. The ability of liposomes to sequester drugs in circulating liposomes and within deep tissue compartments may account for these differences.