中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2010年
6期
432-437
,共6页
郑寅%许钟烨%焦正%朱秋毓%刘骏峰%顾勇%林善锬%郝传明%丁峰
鄭寅%許鐘燁%焦正%硃鞦毓%劉駿峰%顧勇%林善錟%郝傳明%丁峰
정인%허종엽%초정%주추육%류준봉%고용%림선담%학전명%정봉
柠檬酸盐类%药代动力学%连续性肾脏替代治疗
檸檬痠鹽類%藥代動力學%連續性腎髒替代治療
저몽산염류%약대동역학%련속성신장체대치료
Citrates%Pharmacokinetics%Continuous renal replacement therapy
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.
目的 構建連續性腎髒替代治療(CRRT)時枸櫞痠藥物代謝動力學數學模型,併運用該模型預測肝功能異常患者進行跼部枸櫞痠抗凝(RCA)-CRRT時髮生枸櫞痠蓄積的風險.方法 將體外枸櫞痠輸註速度、體內枸櫞痠藥物動力學、體外枸櫞痠透析清除動力學等影響血漿枸櫞痠濃度的參數綜閤,構建一箇服從一室模型、一級消除動力學的枸櫞痠藥物代謝動力學數學模型.運用模型採用文獻報道的肝硬化和非肝硬化危重患者體內枸櫞痠藥物代謝動力學參數,預測枸櫞痠代謝正常、肝功能損害及肝衰竭的患者在實施不同CRRT治療方案時髮生枸櫞痠蓄積的風險.結果 枸櫞痠藥物代謝動力學數學模型:Csys=C(0)·e-[(clb+clf)·t/V]+G/CLb+CLf×(1-e-[(clb+clf)·t/V]).由模型得到的血漿枸櫞痠濃度預測值與文獻報道的實測濃度擬閤理想.根據模型推算,體內枸櫞痠清除正常的患者在接受RCA-CRRT時,血漿枸櫞痠濃度始終□1 mmol/L;噹CRRT抽提分數高于66%時,肝功能異常患者體內枸櫞痠穩態濃度將低于中毒濃度.結論 枸櫞痠藥物代謝動力學模型可預測危重患者在實施RCA-CRRT時髮生枸櫞痠蓄積的風險,併為體內枸櫞痠代謝清除障礙的患者選擇閤適安全的RCA-CRRT方案提供理論依據.
목적 구건련속성신장체대치료(CRRT)시구연산약물대사동역학수학모형,병운용해모형예측간공능이상환자진행국부구연산항응(RCA)-CRRT시발생구연산축적적풍험.방법 장체외구연산수주속도、체내구연산약물동역학、체외구연산투석청제동역학등영향혈장구연산농도적삼수종합,구건일개복종일실모형、일급소제동역학적구연산약물대사동역학수학모형.운용모형채용문헌보도적간경화화비간경화위중환자체내구연산약물대사동역학삼수,예측구연산대사정상、간공능손해급간쇠갈적환자재실시불동CRRT치료방안시발생구연산축적적풍험.결과 구연산약물대사동역학수학모형:Csys=C(0)·e-[(clb+clf)·t/V]+G/CLb+CLf×(1-e-[(clb+clf)·t/V]).유모형득도적혈장구연산농도예측치여문헌보도적실측농도의합이상.근거모형추산,체내구연산청제정상적환자재접수RCA-CRRT시,혈장구연산농도시종□1 mmol/L;당CRRT추제분수고우66%시,간공능이상환자체내구연산은태농도장저우중독농도.결론 구연산약물대사동역학모형가예측위중환자재실시RCA-CRRT시발생구연산축적적풍험,병위체내구연산대사청제장애적환자선택합괄안전적RCA-CRRT방안제공이론의거.
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.
