| Title: |
Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): combined experience from phase I and phase II studies |
| Authors: |
Adedoyin, A; Bernardo, J F; Swenson, C E; Bolsack, L E; Horwith, G; DeWit, S; Kelly, E; Klasterksy, J; Sculier, J P; DeValeriola, D; Anaissie, E; Lopez-Berestein, G; Llanos-Cuentas, A; Boyle, A; Branch, R A |
| Source: |
Antimicrobial Agents and Chemotherapy ; volume 41, issue 10, page 2201-2208 ; ISSN 0066-4804 1098-6596 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
1997 |
| Description: |
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 AmB concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of AmB 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/aac.41.10.2201 |
| DOI: |
10.1128/AAC.41.10.2201 |
| Availability: |
https://doi.org/10.1128/aac.41.10.2201; https://journals.asm.org/doi/pdf/10.1128/AAC.41.10.2201 |
| Rights: |
https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.304DC9E2 |
| Database: |
BASE |