原创力文档pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer药物动力学phenoxodiol,新颖的异黄酮,静脉注射后政府晚期癌症患者.pdfVIP
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pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer药物动力学phenoxodiol,新颖的异黄酮,静脉注射后政府晚期癌症患者
Howes et al. BMC Clinical Pharmacology 2011, 11:1
/1472-6904/11/1
RESEARCH ARTICLE Open Access
Pharmacokinetics of phenoxodiol, a novel
isoflavone, following intravenous administration
to patients with advanced cancer
1 2,4 3 3 1*
Jan B Howes , Paul L de Souza , Leanne West , Li Jiu Huang , Laurence G Howes
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
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