A pharmacodynamic study of docetaxel in combination with the P-glycoprotein antagonist tariquidar (XR9576) in patients with lung, ovarian, and cervical cancer.

ABSTRACT:

Purpose

P-glycoprotein (Pgp) antagonists have been difficult to develop because of complex pharmacokinetic interactions and a failure to show meaningful results. Here we report the results of a pharmacokinetic and pharmacodynamic trial using a third-generation, potent, noncompetitive inhibitor of Pgp, tariquidar (XR9576), in combination with docetaxel.

Experimental design

In the first treatment cycle, the pharmacokinetics of docetaxel (40 mg/m(2)) were evaluated after day 1 and day 8 doses, which were administered with or without tariquidar (150 mg). (99m)Tc-sestamibi scanning and CD56(+) mononuclear cell rhodamine efflux assays were conducted to assess Pgp inhibition. In subsequent cycles, 75 mg/m(2) docetaxel was administered with 150 mg tariquidar every 3 weeks.

Result

SUBMITTER: Kelly RJ 

PROVIDER: S-EPMC3071989 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature