摘要目的 分析利奈唑胺在中国人的群体药代动力学特性.方法 2009年9—12月在北京市招募31名健康志愿者,年龄18~45岁,平均28岁,单次给予利奈唑胺600 mg静脉滴注;2010年1月1日至12月31日收集在解放军总医院住院的呼吸道感染患者57例,年龄21~83岁,平均53岁,给予利奈唑胺600 mg/12 h静脉滴注或口服至少5次.采用高效液相色谱法测定利奈唑胺血浆浓度,应用非线性混合效应模型法建立利奈唑胺群体药代动力学模型,采用Phonex NLME 1.0软件对结果进行统计分析.本研究为开放、无对照、前瞻性平行研究.结果 健康志愿者单次给予利奈唑胺,其基础药代动力学模型为二房室线性消除模型;群体典型值为:中央室分布容积为29.66 L,外周室分布容积为22.22 L,中央室清除率为7.99 L/h,外周室清除率为101.28 L/h;体重与其均值每相差1 kg时外周室分布容积改变0.62 L.感染患者给予利奈唑胺达稳态时,其基础药代动力学模型为一房室线性消除模型;群体典型值的表观分布容积为38.85 L,表观清除率为4.71 L/h;体重与其均值每相差1 kg,分布容积改变0.79 L,清除率改变0.04 L/h;年龄与其均值每相差1岁,清除率改变-0.05 L/h.结论 中国人群利奈唑胺的群体药代动力学特征为:单次给药时为二房室线性模型,体重与表观分布容积呈线性正相关;多次给药时为一房室线性模型;体重与表观分布容积和表观清除率呈线性正相关,年龄与表观清除率呈线性负相关.

abstractsObjective To study the population pharmacokinetic ( PPK ) profiles of linezolid in Chinese healthy volunteers and infected patients .Methods Linezolid 600 mg was administered to 31 Chinese healthy volunteers with a single dose and to 57 infected patients every 12 h for at least 5 doses.High performance liquid chromatography was applied to determine the plasma concentration of linezolid .Nonlinear mixed-effects modeling method was applied to analyze the PPK profiles .Results For healthy volunteers with single dose of linezolid , 2-compartment with linear elimination model was the most appropriate structural pharmacokinetic model.The population typical value of apparent volume of central compartment was 26.99 L, volume of peripheral compartment was 22.22 L, apparent clearance of central compartment was 7.99 L/h, and clearance of peripheral compartment was 101.28 L/h.For each 1 kg deviation of weight from the mean value, 0.62 L of volume of peripheral compartment was correlated .For Chinese infected patients with multiple doses of linezolid , 1-compartment with linear elimination model was the most appropriate structural pharmacokinetic model . The population typical value of apparent volume was 38.85 L, and apparent clearance was 4.70 L/h.For each 1 kg deviation of weight from the mean value , 0.79 L of volume , as well as 0.04 L/h of clearance were correlated .For each 1 year deviation of age from the mean value , -0.045 L/h of clearance was correlated.Conclusions The pharmacokinetic profiles of linezolid in Chinese simulate a 2-compartment with linear elimination model when single dose is administrated , and the weight is linearly positive-correlated to volume.While a 1-compartment with linear elimination model is appropriate when multiple doses are administrated , and the weight is linearly positive-correlated to volume and clearance , but the age is linearly negative-correlated to clearance .