目的 建立中国成年人中服用地高辛患者的群体药动学（ PPK ）模型，促进个体化给药。 方法 收集 155 名长期规律服用地高辛患者的 262 例次稳态地高辛的测定结果以及相关临床数据。应用 NONMEM 软件求算 PPK 参数值，建立基本模型和最终模型。运用内部验证法，验证模型的可靠性。 结果 地高辛达到稳态时，其 PPK 模型符合口服吸收一室模型。地高辛体内清除和患者血清肌酐浓度、体重、是否有合并用钙离子拮抗剂（ CCB ）、螺内酯 (SPR) 有关。最终模型可表达为： <> CL /<>F=9.33 × 0.512(SCR/119.1) × [1+0.017 × (Weight - 61.2)] × (1 - 0.21 × CCB) × (1 - 0.19 × SPR) L·kg-1·h-1 。 <> K a =1.54 h -1 ； <> V d /<>F=187 L 。经内部验证法验证，本模型稳定、可靠。新取 5 个地高辛数据应用本模型进行预测，预测结果与临床实际监测结果相符较好。 结论 用 NONMEM 软件成功建立中国成年人服用地高辛的 PPK 模型。
Abstract
OBJECTIVE To establish population pharmacokinetic model of Digoxin in Chinese adult patients, and set up individualized dose regimen by use of individual pharmacokinetic parameters estimated through the model. METHODS 262 Sparse digoxin serum concentrations were collected from 155 adult patients. Basic models and final models of digoxin were developed by NONMEM software and population pharmacokinetic parameters were acquired. RESULTS Population pharmacokinetic model of digoxin was described as one-compartment model. The serum creatinine level, body weight and coadministration of the calcium antagonist (CCB) or spironolactone (SPR) affected the clearance rate of digoxin concentrations in serum.The parameters of final model of digoxin were as follows: CL/F=9.33×0.512(SCR/119.1) ×[1+0.017×(WEIGHT-61.2)]×(1- 0.21×CCB) ×(1-0.19×SPR) L·kg-1·h-1。Ka=1.54 h-1; Vd/F=187 L. The model was stable and reliable by bootstrap. Good prediction results of digoxin of 5 extra patients were obtained. CONCLUSION Population pharmacokinetic models of digoxin in Chinese adult patients were built successfully by NONMEM software.
关键词
地高辛 /
群体药动学 /
治疗药物监测 /
NONMEM 软件
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Key words
digoxin /
population pharmacokinetics /
therapeutic drug monitoring /
NONMEM software
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参考文献
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（ 收稿日期 ： 2008-11-20 ）
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