Flavone acetic acid: a nonlinear pharmacokinetic model
Flavone acetic acid: a nonlinear pharmacokinetic model
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DOI：
10.1007/bf00257307
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发表时间：
2004
影响因子：
3
通讯作者：
A. Gouyette;D. Kerr;S. Kaye;A. Setanoians;J. Cassidy;C. Bradley;G. Forrest;M. Soukop
中科院分区：
文献类型：
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作者：
A. Gouyette;D. Kerr;S. Kaye;A. Setanoians;J. Cassidy;C. Bradley;G. Forrest;M. Soukop
在I期临床试验中研究了31例患者的黄酮乙酸药代动力学。该药物通过静脉输注给药，剂量范围为0.5 - 6.4 g/m2，持续1、1.5、3和6 h。根据包括Michaelis-Menten型动力学的非线性模型确定药代动力学参数。平均消除半衰期为4.8 h，中央室平均分布容积为7.61。基于“治疗窗”概念，我们的模型预测最大耐受剂量（MTD）为11.1 g/m2，非常接近临床观察到的MTD 10 g/m2。当考虑不同的接种方案时，该模型也是可操作的，例如分次给药方案与独特的输注方案，并且表明在MTD下，应每72小时进行一次注射以避免药物蓄积。
Flavone acetic acid pharmacokinetics were studied in 31 patients in a phase I clinical trial. The drug was given by i.v. infusions over 1, 1.5, 3, and 6 h at doses ranging from 0.5 to 6.4 g/m2. The pharmacokinetic parameters were determined according to a nonlinear model including Michaelis-Menten-type kinetics. The mean elimination half-life is 4.8 h and the mean volume of distribution of the central compartment, 7.61. Our model predicted a maximal tolerated dose (MTD) of 11.1 g/m2on the basis of the “therapeutic window” concept, very close to the clinically observed MTD of 10 g/m2. This model is also operational when different protocols of inoculation are considered, such as a divided-dose schedule vs a unique infusion, and indicates that, at the MTD, injections should be made every 72 h to avoid drug accumulation.