Howes Jan B, de Souza Paul L, West Leanne, Huang Li Jiu, Howes Laurence G
Department of Pharmacology and Therapeutics, Griffith University, Gold Coast Hospital, Southport, Queensland, Australia.
BMC Clin Pharmacol. 2011 Feb 3;11:1. doi: 10.1186/1472-6904-11-1.
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.
苯氧二醇是一种新型异黄酮，目前正在进行治疗癌症的临床试验研究。本研究报告了苯氧二醇在癌症患者中的药代动力学情况。
在单次静脉推注剂量后以及持续静脉输注期间研究苯氧二醇的药代动力学。3名前列腺癌男性患者和3名乳腺癌女性患者接受静脉推注苯氧二醇（5mg/kg），采集血浆样本检测游离和总苯氧二醇水平。在另一个时间点，5名相同患者接受苯氧二醇持续静脉输注（2mg/kg/h），再次采集血浆样本检测游离和总苯氧二醇水平。使用带紫外检测的梯度高效液相色谱法测定苯氧二醇。
推注给药后，游离和总苯氧二醇似乎遵循一级药代动力学。游离和总苯氧二醇的消除半衰期分别为0.67±0.53小时和3.19±1.93小时，而总血浆清除率分别为2.48±2.33L/h和0.15±0.08L/h。各自的表观分布容积分别为1.55±0.69L/kg和0.64±0.51L/kg。在持续静脉输注期间，游离苯氧二醇迅速蓄积，在0.87±0.18小时后达到稳态平均浓度0.79±0.14μg/ml。游离苯氧二醇的表观蓄积半衰期为0.17±0.04小时，而持续输注期间的血浆清除率为1.29±0.23L/h。
苯氧二醇的血浆半衰期较短，尤其是游离形式，这导致在持续静脉输注期间能迅速达到稳态水平。
澳大利亚新西兰临床试验注册中心（ANZCTR）：ACTRN12610000334000。
