POPULATION ANALYSIS OF THE PHARMACOKINETIC VARIABILITY OF HIGH-DOSE METOCLOPRAMIDE IN CANCER-PATIENTS
POPULATION ANALYSIS OF THE PHARMACOKINETIC VARIABILITY OF HIGH-DOSE METOCLOPRAMIDE IN CANCER-PATIENTS
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DOI：
10.2165/00003088-198814010-00004
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发表时间：
1988-01-01
影响因子：
4.5
通讯作者：
BATEMAN, DN
中科院分区：
文献类型：
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作者：
GREVEL, J;WHITING, B;BATEMAN, DN
甲氧氯普胺输注用于预防癌症患者化疗期间的恶心和呕吐。47例患者在109次化疗期间接受甲氧氯普胺作为负荷（剂量范围= 0.55至4.5 mg/kg，15分钟）和维持（剂量范围= 0.57至4.8 mg/kg，8小时）输注。在维持输注期间和结束后24小时内，每次治疗采集4 - 10份血样。通过液相色谱法分析血浆中的甲氧氯普胺。使用线性二室模型，通过NONMEM程序分析了83种治疗的药代动力学和人口统计学数据。结果发现，体重和血清碱性磷酸酶活性解释了清除率（CL）的一些个体间变异性。平均个体（70 kg，碱性磷酸酶= 100 IU/L）的典型药代动力学参数为：CL = 20 L/h;稳态分布容积（Vdss）= 190 L;终末半衰期= 8 h。清除率、中央室容积和Vdss的个体间变异性分别为50%、35%和35%。血浆浓度的残差变异性估计为13%。
Metoclopramide infusions are used to prevent nausea and vomiting in cancer patients during chemotherapy. 47 patients received metoclopramide during 109 chemotherapeutic treatments as a loading (dose range = 0.55 to 4.5 mg/kg over 15 minutes) and maintenance (dose range = 0.57 to 4.8 mg/kg over 8 hours) infusion. During and up to 24 hours after the end of the maintenance infusion between 4 and 10 blood samples were collected per tratment. Metoclopramide was analyzed in plasma by liquid chromatography. Pharmacokinetic and demographic data of 83 treatments were analyzed by the NONMEM program using a linear 2-compartment model. It was found that body weight and serum alkaline phosphatase activity explain some of the interindividual variability in clearance (CL). The typical pharmacokinetic parameters for an average individual (70kg, alkaline phosphatase = 100 IU/L) were: CL = 20 L/h; volume of distriubtion at steady state (Vdss) = 190L; terminal half-life = 8h. The interindividual variabilities in clearance, volume of central compartment and Vdss were 50%, 35% and 35%, respectively. The residual variability in plasma concentrations was estimated as 13%.