论文部分内容阅读
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。Ka=1.54h-1;Vd/F=187L。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。
Objective To establish a population pharmacokinetics (PPK) model of digoxin patients in Chinese adults to promote individualized administration. Methods The data of 262 sub-steady-state digoxin determinations and clinical data of 155 long-term regular digoxin patients were collected. Applying NONMEM software to calculate PPK parameter values, establishing the basic model and the final model. Use the internal verification method to verify the reliability of the model. Results When digoxin reached its steady state, its PPK model was consistent with the oral absorption one-compartment model. In vivo clearance of digoxin and serum creatinine concentration, body weight, whether combined with calcium antagonists (CCB), spironolactone (SPR) related. The final model can be expressed as: 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 = 1.54h-1; Vd / F = 187L. The internal verification method verified that the model is stable and reliable. Five new digoxin data were applied to predict this model. The predicted results are in good agreement with the actual clinical monitoring results. Conclusions The Chinese model of PPK using digoxin was established successfully by NONMEM software.