CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity.

ABSTRACT:

Purpose

Paclitaxel is used for the treatment of several solid tumors and displays a high interindividual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity.

Experimental design

In an exploratory cohort of patients (n = 261) treated with paclitaxel, neurotoxicity incidence, and severity, pharmacokinetic parameters and pharmacogenetic variants were determined. Paclitaxel plasma concentrations were measured by high-performance liquid chromatography or liquid chromatography/tandem mass spectrometry, and individual pharmacokinetic parameters were estimated from previously developed population

SUBMITTER: de Graan AJ 

PROVIDER: S-EPMC3686845 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature