连续性肾脏替代治疗时枸橼酸药物代谢动力学数学模型的构建  

Establishment of a citrate pharmacokinetics model and its application in RCA-CRRT

作　　者：郑寅 许钟烨 焦正 朱秋毓 刘骏峰 顾勇 林善锬 郝传明 丁峰 

机构地区：[1]复日大学附属华山医院肾脏科,上海200040 [2]复日大学附属华山医院临床药学研究室,上海200040

出　　处：《中华肾脏病杂志》2010年第6期432-437,共6页Chinese Journal of Nephrology

基　　金：上海市科学技术委员会资助项目（09411961500）

摘　　要：目的 构建连续性肾脏替代治疗（CRRT）时枸橼酸药物代谢动力学数学模型,并运用该模型预测肝功能异常患者进行局部枸橼酸抗凝（RCA）-CRRT时发生枸橼酸蓄积的风险.方法 将体外枸橼酸输注速度、体内枸橼酸药物动力学、体外枸橼酸透析清除动力学等影响血浆枸橼酸浓度的参数综合,构建一个服从一室模型、一级消除动力学的枸橼酸药物代谢动力学数学模型.运用模型采用文献报道的肝硬化和非肝硬化危重患者体内枸橼酸药物代谢动力学参数,预测枸橼酸代谢正常、肝功能损害及肝衰竭的患者在实施不同CRRT治疗方案时发生枸橼酸蓄积的风险.结果 枸橼酸药物代谢动力学数学模型： Csys=C（0）·e^-[（clb＋clf）·t/V]＋G/CLb＋CLf×（1-e^-[（clb＋clf）·t/V]）.由模型得到的血浆枸橼酸浓度预测值与文献报道的实测浓度拟合理想.根据模型推算,体内枸橼酸清除正常的患者在接受RCA-CRRT时,血浆枸橼酸浓度始终□1 mmol/L;当CRRT抽提分数高于66%时,肝功能异常患者体内枸橼酸稳态浓度将低于中毒浓度.结论 枸橼酸药物代谢动力学模型可预测危重患者在实施RCA-CRRT时发生枸橼酸蓄积的风险,并为体内枸橼酸代谢清除障碍的患者选择合适安全的RCA-CRRT方案提供理论依据.Objective To establish a citrate pharmacokinetics model which is applied to evaluate the risk of citrate accumulation in patients with liver dysfunction in the continuous renal replacement treatment （CRRT） with regional citrate anticoagulation （RCA）. Methods The source of citrate for extracorporeal anticoagulation, the body clearance and filter elimination of citrate, which were the three major citrate fluxes of systemic citrate level, were combined into a single-pool, first order kinetic equation. The data from a published clinical study of systemic citrate kinetics in the intensive care unit patients with or without liver cirrhosis were adapted and the citrate kinetic equation was applied to predict the risk of systemic citrate accumulation in patients with normal, impaired and absent liver clearance while different RCA-CRRT protocols were carried out. Results The single pool, first order citrate kinetic modeling equation was as follows： Csys=C（0）·e^-[（clb＋clf）·t/V]＋G/CLb＋CLf×（1-e^-[（clb＋clf）·t/V]）There was excellent agreement between published citrate measurements and our predictions. Kinetic modeling showed that the plasma citrate concentration of patients with normal citrate body clearance was no more than 1 mmol/L during common RCA-CRRT. The model predicted that when the single pass fractional extraction of citrate on the artificial kidney was above 66%, systemic steady citrate concentration would be among the safe range even in patients of impaired body metabolism of citrate.Conclusions The citrate kinetic model of RCA-CRRT can predict the risk of systemic citrate accumulation and provide the basis for designing the safe RCA-protocols for the patients with impaired body clearance of citrate.

关 键 词：柠檬酸盐类 药代动力学 连续性肾脏替代治疗 

分 类 号：R96[医药卫生—药理学]