Pharmacokinetics and pharmacodynamics of nab-paclitaxel in patients with solid tumors: disposition kinetics and pharmacology distinct from solvent-based paclitaxel

J Clin Pharmacol. 2014 Oct;54(10):1097-107. doi: 10.1002/jcph.304. Epub 2014 Apr 9.


The aim of this study was to characterize population pharmacokinetics and the exposure-neutropenia relationship with nanoparticle albumin-bound (nab)-paclitaxel in patients with solid tumors. Plasma and blood concentrations of paclitaxel and neutrophil data were collected from 150 patients with various solid tumors over the nab-paclitaxel dose range of 80-375 mg/m(2). Data were analyzed using nonlinear mixed-effect modeling or logistic regression. Pharmacokinetics of nab-paclitaxel were described by a 3-compartment model with saturable distribution and elimination. The rapid disappearance of circulating paclitaxel was driven by its fast distribution to peripheral compartments; maximum rate for saturable distribution (325000 μg/h) was 40-fold greater than that for saturable elimination (8070 μg/h). Albumin was a significant covariate of paclitaxel elimination (P < .001), while total bilirubin, creatinine clearance, body size, age, sex, and tumor type had no significant or clinically relevant effect. The probability of experiencing a ≥ 50% reduction in neutrophils was best correlated to the duration above the drug concentration of 720 ng/mL. At a given exposure level, neutropenia development was positively correlated with increasing age but not significantly influenced by hepatic function, tumor type, sex, or dosing schedule. Covariate analyses supports exposure-matched dose adjustments in patients with moderate to severe hepatic impairment.

Keywords: covariates; nab-paclitaxel; neutropenia; pharmacodynamics; pharmacokinetics.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Albumins / administration & dosage*
  • Albumins / pharmacokinetics
  • Albumins / pharmacology
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Liver Diseases / physiopathology
  • Logistic Models
  • Male
  • Middle Aged
  • Models, Biological*
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced
  • Neutropenia / epidemiology
  • Nonlinear Dynamics
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / pharmacology
  • Young Adult


  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antineoplastic Agents, Phytogenic
  • Paclitaxel