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

source extracted confidence: high 2026-04-09
#albumins #antineoplastic-agents-phytogenic #chemistry-pharmaceutical #delayed-action-preparations #drug-carriers

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

Ait-Oudhia et al., 2012 | Pharm Res | Meta Analysis

Citation

Ait-Oudhia Sihem, Straubinger Robert M, Mager Donald E. Meta-analysis of nanoparticulate paclitaxel delivery system pharmacokinetics and model prediction of associated neutropenia. Pharm Res. 2012-Oct;29(10):2833-44. doi:10.1007/s11095-012-0775-8

Abstract

PURPOSE: 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. METHODS: 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. RESULTS: 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 predicted remarkably well the clinically-observed relationships between neutropenia and free drug exposure relative to a threshold concentration. CONCLUSIONS: Paclitaxel disposition was well-described for all formulations. The derived model predicts toxicodynamics of diverse paclitaxel carriers.

Key Findings

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 predicted remarkably well the clinically-observed relationships between neutropenia and free drug exposure relative to a threshold concentr

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Albumins
  • Antineoplastic Agents, Phytogenic
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Carriers
  • Drug Delivery Systems
  • Humans
  • Liposomes
  • Nanoparticles
  • Neutropenia
  • Paclitaxel
  • Polyethylene Glycols
  • Tocopherols

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
  • Vertical: vitamin-e

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09