文拉法辛在闽南抑郁症患者中的群体药动学

Population pharmacokinetics research of venlafaxine in Southern Fujian depression patients

目的建立闽南人群抑郁症患者口服文拉法辛的药动学模型,为临床个体化给药方案提供参考。方法以69例服用文拉法辛的闽南抑郁症患者为研究对象,采集了152个稳态血样资料,以高效液相色谱法测定血药浓度,同时收集患者的临床和实验室检查等资料,运用非线性混合效应模型,建立文拉法辛的群体药动学模型;考察各项因素对药动学参数的影响,并以Bootstrap法进行模型验证。结果一级吸收和消除模型能够较好地模拟文拉法辛的体内过程,在所有因素中,体重对表观分布容积有影响,肌酐清除率对表观清除率有影响,文拉法辛表观清除率和表观分布容积的群体典型值分别为83.7 L·h-1和343 L。结论建立了闽南抑郁症患者口服文拉法辛的群体药动学模型,模型经验证稳定可靠。

AIM To set up a population pharmacokinetic （PPK） model of venlafaxine in Southern Fujian people, and provide a reasonable use of venlafaxine in clinical practice. METHODS Totally 69 depression patients were orally administered with venlafaxine, and 152 blood samples were collected. The laboratory parameters and clinical data were collected and the plasma concentration was determined by HPLC. Nonlinear mixed effect modeling （NONMEM） was employed to establish the PPK model. The effects of various factors on the pharmaeokinetie parameters were estimated and the final PPK model was validated by Bootstrap method. RESULTS The pharmaeokinetic profile of venlafaxine was best described by a one- compartment model with first- order absorption and elimination. Body weight affected the distribution volume, and ereatinine showed influence on clearance. The population typical values of CL （F） and Vd were 83.7 L ·h^-1 and 343 L, respectively. CONCLUSION The PPK model of venlafaxine in southern Fujian depression patients has been established in the study, and the PPK model is proved to be robust and reliable.