Display Settings:

Format

Send to:

Choose Destination
Pharmacogenomics J. 2011 Apr;11(2):113-20. doi: 10.1038/tpj.2010.19. Epub 2010 Apr 6.

Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer.

Author information

  • 1Department of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark. tbergmann@health.sdu.dk

Abstract

The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h⁻¹ (range 176-726 l h⁻¹). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P=0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P=0.04) and ABCC1 g.7356253C>G (P=0.04).

PMID:
20368717
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk