%0 Journal Article
%T Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer
%A Jan B Howes
%A Paul L de Souza
%A Leanne West
%A Li Huang
%A Laurence G Howes
%J BMC Pharmacology and Toxicology
%D 2011
%I BioMed Central
%R 10.1186/1472-6904-11-1
%X The pharmacokinetics of phenoxodiol was studied following a single intravenous (iv) bolus dose and during a continuous intravenous infusion. Three men with prostate cancer and 3 women with breast cancer received IV bolus phenoxodiol (5 mg/kg) and plasma was sampled for free and total phenoxodiol levels. On a separate occasion 5 of the same patients received a continuous intravenous infusion of phenoxodiol (2 mg/kg/h) and plasma was again sampled for free and total phenoxodiol levels. Phenoxodiol was measured using gradient HPLC with ultraviolet detection.Following bolus injection, free and total phenoxodiol appeared to follow first order pharmacokinetics. The elimination half-lives for free and total phenoxodiol were 0.67 ¡À 0.53 h and 3.19 ¡À 1.93 h, respectively, while the total plasma clearance rates were 2.48 ¡À 2.33 L/h and 0.15 ¡À 0.08 L/h, respectively. The respective apparent volumes of distribution were 1.55 ¡À 0.69 L/kg and 0.64 ¡À 0.51 L/kg. During continuous intravenous infusion, free phenoxodiol accumulated rapidly to reach a mean concentration at steady state of 0.79 ¡À 0.14 ¦Ìg/ml after 0.87 ¡À 0.18 h. The apparent accumulation half-life of free phenoxodiol was 0.17 ¡À 0.04 h while the plasma clearance during continuous infusion was 1.29 ¡À 0.23 L/h.Phenoxodiol has a short plasma half-life, particularly in the free form, leading to a rapid attainment of steady state levels during continuous intravenous infusion.Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000334000Phenoxodiol (PXD, NV-06) is an isoflavone derivative that has been demonstrated in vitro and in vivo to possess anti-cancer activity [1-9]. Phenoxodiol is a synthetic analogue of genistein with unknown mechanism of action. It appears to have pleiotropic actions such as inhibition of tyrosine kinases, inhibition of topoisomerase II in a dose-dependent manner and inhibition of the X-linked inhibitor of apoptosis [2,10-12] but the predominant mode of action remains to be elucidated.
%U http://www.biomedcentral.com/1472-6904/11/1