Zhang L, Bai N, Liu Y N, Wang R
*Department of Pulmonary & Critical Care Medicine, General Hospital of Chinese People Liberation Army, Beijing 100853, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2016 Dec 12;39(12):924-928. doi: 10.3760/cma.j.issn.1001-0939.2016.12.004.
To study the population pharmacokinetic (PPK) profiles of linezolid in Chinese healthy volunteers and infected patients. 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. 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. 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.
研究利奈唑胺在中国健康志愿者和感染患者中的群体药代动力学（PPK）特征。对31名中国健康志愿者单次给予600 mg利奈唑胺，对57名感染患者每12小时给药一次，至少给药5剂。采用高效液相色谱法测定利奈唑胺的血浆浓度。应用非线性混合效应建模方法分析PPK特征。对于单次给予利奈唑胺的健康志愿者，二室线性消除模型是最合适的结构药代动力学模型。中央室表观容积的群体典型值为26.99 L，周边室容积为22.22 L，中央室表观清除率为7.99 L/h，周边室清除率为101.28 L/h。体重每偏离平均值1 kg，周边室容积相关变化0.62 L。对于多次给予利奈唑胺的中国感染患者，一室线性消除模型是最合适的结构药代动力学模型。表观容积的群体典型值为38.85 L，表观清除率为4.70 L/h。体重每偏离平均值1 kg，容积相关变化0.79 L，清除率相关变化0.04 L/h。年龄每偏离平均值1岁，清除率相关变化 -0.045 L/h。利奈唑胺在中国的药代动力学特征在单次给药时模拟二室线性消除模型，体重与容积呈线性正相关。而多次给药时一室线性消除模型合适，体重与容积和清除率呈线性正相关，但年龄与清除率呈线性负相关。
