目的 評價卡培他濱在腸癌患者的群體藥動學(xué)特征及可能的影響因素。方法 選取56例腸癌（包括結(jié)腸癌及直腸癌）患者為研究對象，餐后單次口服卡培他濱 0.6 g（0.15 g×4片）后進行多點采集血樣，以高效液相色譜-質(zhì)譜聯(lián)用法（HPLC-MS/MS）檢測受試者給藥后血漿中的卡培他濱的血藥濃度，以非線性混合效應(yīng)模型及程序（NONMEM）對檢測數(shù)據(jù)進行分析，建立卡培他濱群體藥動學(xué)模型并獲得其群體藥動學(xué)參數(shù)。結(jié)果 最終模型為一級吸收和消除的一室模型，模型的藥動學(xué)參數(shù)群體典型值為：清除率（CL）為265 L/h，表觀分布容積（V）為329 L，吸收速率常數(shù)（K_a）為2.15 h⁻¹。人口統(tǒng)計學(xué)因素（年齡、性別、體質(zhì)量等）及肝腎清除相關(guān)因素（肌酐清除率、膽紅素及白蛋白等）對卡培他濱的清除均無顯著性影響。結(jié)論 所得模型穩(wěn)定，能較好地擬合卡培他濱在腸癌患者的的群體藥動學(xué)特征，可用于臨床個體化給藥方案的制訂。

Objective To investigate the population pharmacokinetic characteristics of capecitabine and its possible influencing factors in colorectal cancer patients.Methods 56 colorectal cancer patients were chosen as the research objects. After a single dose of 0.6 g (0.15 g, 4 tablets, orally) of capecitabine tablets, blood samples were collected from multiple sites, the plasma concentration of capecitabine was determined by HPLC-MS/MS. The nonlinear mixed effect model and program (NONMEM) were used to analyze the data, the population pharmacokinetic model of capecitabine was established and its population pharmacokinetic parameters were obtained.Results The final model is one-compartment model with first order absorption and elimination. Population typical pharmacokinetic parameters of the model: clearance (CL) is 265 L/h, apparent volume of distribution (V) is 329 L, and the absorption rate constant (K_a) is 2.15 h⁻¹. Demographic factors (age, gender, body weight, etc.) and liver kidney clearance related factors (creatinine clearance rate, bilirubin and albumin, etc.) have no significant effect on the clearance of capecitabine.Conclusion The model is stable and can well fit the population pharmacokinetic characteristics of capecitabine in Chinese patients with colorectal cancer, which can be used for developing a individualized administration scheme in clinical.

R969.1

國家自然科學(xué)基金-河南人才培養(yǎng)聯(lián)合基金資助項目（U1204818）；河南省科技計劃項目（172102310064）