NDLI: Dual Physiologically Based Pharmacokinetic Model of Liposomal and Nonliposomal Amphotericin B Disposition

Content Provider	Springer Nature Link
Author	Kagan, Leonid Gershkovich, Pavel Wasan, Kishor M. Mager, Donald E.
Copyright Year	2013
Abstract	To investigate the biodistribution of amphotericin B (AmB) in mice and rats following administration of liposomal AmB (AmBisome®) using a physiologically-based pharmacokinetic (PBPK) modeling framework and to utilize this approach for predicting AmBisome® pharmacokinetics in human tissues.AmB plasma and tissue concentration-time data, following single and multiple intravenous administration of nonliposomal and liposomal AmB to mice and rats, were extracted from literature. The whole-body PBPK model was constructed and incorporated nonliposomal and liposomal subcompartments. Various structural models for individual organs were evaluated. Allometric relationships were incorporated into the model to scale parameters based on species body weight.A non-Michaelis-Menten mechanism was included into the structure of the liver and spleen liposomal compartments to describe saturable uptake of particles by the reticuloendothelial system. The model successfully described plasma and tissue pharmacokinetics of AmB after administration of AmBisome® to rats and mice.The dual PBPK model demonstrated good predictive performance by reasonably simulating AmB exposure in human tissues. This modeling framework can be potentially utilized for optimizing AmBisome® therapy in humans and for investigating pathophysiological factors controlling AmB pharmacokinetics and pharmacodynamics.
Starting Page	35
Ending Page	45
Page Count	11
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	31
Issue Number	1
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2013-06-21
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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