PHARMACOKINETIC PROFILE OF ABELCET (AMPHOTERICIN-B LIPID COMPLEX INJECTION) - COMBINED EXPERIENCE FROM PHASE-I AND PHASE-II STUDIES

Amphotericin B (AmB) has been the most effective systemic antifungal a gent, but its use is limited by the dose-limiting toxicity of the conv entional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and incl ude ABELCET (formerly ABLC), but their dispositions have not been well characterized; hence, the reason for their improved profiles remains unclear. This report details the pharmacokinetics of ABELCET examined in various pharmacokinetic and efficacy studies by using whole-blood m easurements of AmB concentration performed by high-pressure liquid chr omatography. The data indicated that the disposition of AmB after admi nistration of ABELCET is different from that after administration of F ungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interind ividual variability, extensive distribution, and low clearance. The ph armacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple do sings increased less than proportionately with dose, steady state appe ared to have been attained in 2 to 3 days, despite an estimated half-l ife of up to 5 days, and there was no evidence of significant accumula tion in the blood. The data are internally consistent, even though the y were gathered under different conditions and circumstances. The phar macokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for i ts improved toxicity profile compared to those of conventional formula tions.