Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer
1 Department of Pharmacology and Therapeutics, Griffith University, Gold Coast Hospital, Southport, Queensland, 4215 Australia
2 Cancer Pharmacology and Therapeutics Lab, St. George Hospital Clinical School, Kogarah, NSW, 2217 and University of NSW, Australia
3 Marshall - Edwards Pty Ltd, 140 Wicks Rd. North Ryde, NSW, Australia
4 University of Western Sydney Medical School, Campbelltown, NSW 2560, Australia
BMC Clinical Pharmacology 2011, 11:1 doi:10.1186/1472-6904-11-1Published: 3 February 2011
Phenoxodiol is a novel isoflavone currently being studied in clinical trials for the treatment of cancer. This study reports the pharmacokinetics of phenoxodiol in patients with cancer.
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 ± 0.53 h and 3.19 ± 1.93 h, respectively, while the total plasma clearance rates were 2.48 ± 2.33 L/h and 0.15 ± 0.08 L/h, respectively. The respective apparent volumes of distribution were 1.55 ± 0.69 L/kg and 0.64 ± 0.51 L/kg. During continuous intravenous infusion, free phenoxodiol accumulated rapidly to reach a mean concentration at steady state of 0.79 ± 0.14 μg/ml after 0.87 ± 0.18 h. The apparent accumulation half-life of free phenoxodiol was 0.17 ± 0.04 h while the plasma clearance during continuous infusion was 1.29 ± 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): ACTRN12610000334000