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  • Pharmacokinetics of phenoxodiol, a novelisoflavone, following intravenous administration to patients with advanced cancer

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    Author(s)
    Howes, JB
    de Souza, PL
    West, L
    Huang, LJ
    Howes, LG
    Griffith University Author(s)
    Howes, Laurence G.
    Year published
    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) ...
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    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 ᠰ.53 h and 3.19 ᠱ.93 h, respectively, while the total plasma clearance rates were 2.48 ᠲ.33 L/h and 0.15 ᠰ.08 L/h, respectively. The respective apparent volumes of distribution were 1.55 ᠰ.69 L/kg and 0.64 ᠰ.51 L/kg. During continuous intravenous infusion, free phenoxodiol accumulated rapidly to reach a mean concentration at steady state of 0.79 ᠰ.14 姯ml after 0.87 ፊ0.18 h. The apparent accumulation half-life of free phenoxodiol was 0.17 ᠰ.04 h while the plasma clearance during continuous infusion was 1.29 ᠰ.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.
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    Journal Title
    BMC Clinical Pharmacology
    Volume
    11
    Issue
    1
    Publisher URI
    http://www.biomedcentral.com/1472-6904/11/1
    Copyright Statement
    © 2011 Howes et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Note
    Page numbers are not for citation purposes. Instead, this article has the unique article number of 1.
    Subject
    Pharmacology and pharmaceutical sciences
    Publication URI
    http://hdl.handle.net/10072/44930
    Collection
    • Journal articles

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