TY - JOUR
T1 - Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection)
T2 - Combined experience from phase I and phase II studies
AU - Adedoyin, Adedayo
AU - Bernardo, José F.
AU - Swenson, Christine E.
AU - Bolsack, Lois E.
AU - Horwith, Gary
AU - DeWit, Stephane
AU - Kelly, Edward
AU - Klasterksy, J.
AU - Sculier, J. P.
AU - DeValeriola, D.
AU - Anaissie, Elias
AU - Lopez-Berestein, Gabriel
AU - Llanos-Cuentas, Alejandro
AU - Boyle, Anthony
AU - Branch, Robert A.
PY - 1997/10
Y1 - 1997/10
N2 - Amphotericin B (AmB) has been the most effective systemic antifungal agent, but its use is limited by the dose-limiting toxicity of the conventional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and include 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 measurements of Arab concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of Arab after administration of ABELCET is different from that after administration of Fungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interindividual variability, extensive distribution, and low clearance. The pharmacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple dosings increased less than proportionately with dose, steady state appeared to have been attained in 2 to 3 days, despite an estimated half-life of up to 5 days, and there was no evidence of significant accumulation in the blood. The data are internally consistent, even though they were gathered under different conditions and circumstances. The pharmacokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for its improved toxicity profile compared to those of conventional formulations.
AB - Amphotericin B (AmB) has been the most effective systemic antifungal agent, but its use is limited by the dose-limiting toxicity of the conventional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and include 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 measurements of Arab concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of Arab after administration of ABELCET is different from that after administration of Fungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interindividual variability, extensive distribution, and low clearance. The pharmacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple dosings increased less than proportionately with dose, steady state appeared to have been attained in 2 to 3 days, despite an estimated half-life of up to 5 days, and there was no evidence of significant accumulation in the blood. The data are internally consistent, even though they were gathered under different conditions and circumstances. The pharmacokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for its improved toxicity profile compared to those of conventional formulations.
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U2 - 10.1128/aac.41.10.2201
DO - 10.1128/aac.41.10.2201
M3 - Article
C2 - 9333048
AN - SCOPUS:0030827228
SN - 0066-4804
VL - 41
SP - 2201
EP - 2208
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 10
ER -