Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Chemother Pharmacol. 2010 Feb;65(3):563-70. doi: 10.1007/s00280-009-1065-y. Epub 2009 Jul 15.

Effect of rifampin on the pharmacokinetics of Axitinib (AG-013736) in Japanese and Caucasian healthy volunteers.

Author information

1
Pfizer Oncology, Pfizer Global Research and Development, La Jolla Laboratories, 101646 Science Center Drive, San Diego, CA 92121, USA. yazdi.pithavala@pfizer.com

Abstract

PURPOSE:

Axitinib, a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, 3, is metabolized by cytochrome P450 3A4 and glucuronidation. This study evaluated the effect of rifampin, a potent inducer of drug-metabolizing enzymes, on axitinib plasma pharmacokinetics. Equal numbers of Japanese and Caucasian subjects were enrolled to assess the potential differences in axitinib pharmacokinetics between the two ethnicities.

METHODS:

Forty healthy volunteers were randomized to receive 5 mg axitinib alone and with 600 mg rifampin.

RESULTS:

Rifampin expectedly decreased AUCinf and Cmax of axitinib (geometric mean reduced by 79 and 71%, respectively). However, differences in axitinib pharmacokinetics were not observed between Japanese and Caucasian subjects (geometric mean ratios for axitinib treatment alone for AUCinf and Cmax were 103 and 96%).

CONCLUSIONS:

The results support a common axitinib starting dose in both populations. Potent inducers of drug-metabolizing enzymes reduce axitinib exposure and dose adjustments may be needed for optimal efficacy.

PMID:
19603168
PMCID:
PMC2797436
DOI:
10.1007/s00280-009-1065-y
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer Icon for PubMed Central
    Loading ...
    Support Center