Meta-analysis of nanoparticulate paclitaxel delivery system pharmacokinetics and model prediction of associated neutropenia.

Pharmaceutical Research
Sihem Ait-OudhiaDonald E Mager

Abstract

Nanoparticulate paclitaxel carriers have entered clinical evaluation as alternatives to the Cremophor-based standard Taxol(®) (Cre-pac). Their pharmacokinetics (PK) is complex, and factors influencing their pharmacodynamics (PD) are poorly understood. We aimed to develop a unified quantitative model for 4 paclitaxel carriers that captures systems-level PK, predicts micro-scale PK processes, and permits correlations between carrier properties and observed PD. Data consisting of 54 PK profiles and 574 observations were extracted from 20 clinical studies investigating Cre-pac, albumin-(A-pac), liposome-(L-pac), and tocopherol-(T-pac) nanocarriers. A population-PK approach was used for data analysis. All datasets were simultaneously fitted to produce a unified model. Model-based simulations explored relationships between predicted PK and myelosuppression for each formulation. The final model employed nonlinear drug-binding mechanisms to describe Cre-pac and a delayed-release model for A-pac, L-pac, and T-pac. Estimated drug-release rate constants (h(-1)): Cre-pac (5.19), L-pac (1.26), A-pac (0.72), T-pac (0.74). Simulations of equivalent dosing schemes ranked neutropenia severity (highest to lowest): T-pac~Cre-pac>L-pac~A-pac and p...Continue Reading

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Citations

Nov 2, 2012·The Journal of Pharmacology and Experimental Therapeutics·Sihem Ait-OudhiaDonald E Mager
Jul 23, 2014·Critical Reviews in Oncology/hematology·A ViúdezM Hidalgo
Aug 8, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Christin P HollisTonglei Li
Aug 16, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Luciana GiodiniGiuseppe Toffoli
May 17, 2018·Expert Review of Clinical Pharmacology·Anne RodallecJoseph Ciccolini
Jan 1, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jason A Sprowl, Alex Sparreboom
Oct 26, 2018·Expert Opinion on Drug Metabolism & Toxicology·Anne RodallecJoseph Ciccolini
Jan 12, 2020·European Journal of Clinical Pharmacology·Wenjun ChenTianyan Zhou
Jan 1, 2017·The Journal of Antimicrobial Chemotherapy·Michael J Dolton, David Z D'Argenio
Apr 20, 2018·Journal of Pharmacokinetics and Pharmacodynamics·Xiaowei Zang, Leonid Kagan
Aug 7, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wen Wee Ma, Manuel Hidalgo
Apr 24, 2014·Cancer Research·Annemieke J M NieuweboerAlex Sparreboom

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