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BMC Clinical Pharmacology
Published in: BMC Clinical Pharmacology 1/2011

Open Access 01-12-2011 | Research article

Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer

Authors: Jan B Howes, Paul L de Souza, Leanne West, Li Jiu Huang, Laurence G Howes

Published in: BMC Clinical Pharmacology | Issue 1/2011

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000334​000
Appendix
Available only for authorised users
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Metadata
Title
Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer
Authors
Jan B Howes
Paul L de Souza
Leanne West
Li Jiu Huang
Laurence G Howes
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Clinical Pharmacology / Issue 1/2011
Electronic ISSN: 1472-6904
DOI
https://doi.org/10.1186/1472-6904-11-1

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