Population pharmacokinetics of short intravenous vinorelbine infusions in patients with metastatic breast cancer
Population pharmacokinetics of short intravenous vinorelbine infusions in patients with metastatic breast cancer
复制标题
转移性乳腺癌患者短期静脉输注长春瑞滨的群体药代动力学
DOI：
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发表时间：
2004
影响因子：
3
通讯作者：
S. Urien
中科院分区：
文献类型：
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作者：
R. Déporte;N. Simon;P. Fumoleau;M. Campone;P. Kerbrat;J. Bonneterre;P. Fargeot;S. Urien
目的建立长春瑞滨在转移性乳腺癌患者中的群体药代动力学模型。在18 h内采集血样。采用HPLC法测定长春瑞滨的血浆浓度。使用非线性混合效应模型方法进行群体药代动力学分析。结果长春瑞滨浓度-时间曲线最好用三室开放模型描述。血浆清除率（CL）较高，与瘦体重（LBW）和体表面积（BSA）或身高和体重（BW）的组合呈正相关。血清碱性磷酸酶升高对CL有负面影响。CL和中央分布容积（V1）的典型群体估计值分别为74.2 l/h和7.8 l。CL和V1的个体间群体变异系数分别为17.0%和32.0%。最终的人口药代动力学模型的稳定性和预测性能进行了评估，使用200引导样品的原始data.ConclusionThis研究确定了BSA和血清碱性磷酸酶清除率的联合作用。这些结果部分支持基于BSA的长春瑞滨常规剂量调整，但建议在血清碱性磷酸酶极端值的情况下进行剂量调整。
PurposeTo develop a population pharmacokinetic model of vinorelbine administered by short intravenous infusion in metastatic breast cancer patients.MethodsVinorelbine was administered as infusions of 5–10 min at 15, 20 or 25 mg/m2 to 30 patients. Blood samples were collected over 18 h. Plasma concentrations of vinorelbine were determined by HPLC. Population pharmacokinetic analysis was performed using a nonlinear mixed effects modeling method.ResultsVinorelbine concentration-time profiles were best described by a three-compartment open model. Plasma clearance (CL) was high and positively related to lean body weight (LBW) and body surface area (BSA) or to a combination of height and body weight (BW). Elevated serum alkaline phosphatases had a negative effect on CL. Typical population estimates of CL and central distribution volume (V1) were 74.2 l/h and 7.8 l, respectively. The interindividual population coefficients of variation for CL and V1 were 17.0% and 32.0%, respectively. The stability and predictive performance of the final population pharmacokinetic model were assessed using 200 bootstrap samples of the original data.ConclusionThis study identified combined effects of BSA and serum alkaline phosphatases on clearance. These results partly support the conventional dose adjustment of vinorelbine based on BSA, but suggest dose modification in cases of extreme values of serum alkaline phosphatases.