摘要
目的:探讨体外膜肺氧合治疗(ECMO)对重症感染患者达托霉素药动学/药效学(PK/PD)的影响。方法:入选24位重症感染患者其中ECMO组和非ECMO组各12例,静脉滴注达托霉素500 mg qd,待药物达稳后于不同时间点采集静脉血,测定血药浓度,计算并比较组间药代动力学参数,使用蒙特卡罗模拟评估达托霉素相同给药剂量下在不同人群中的靶向达成概率(PTA),通过应用耐甲氧西林金黄色葡萄球菌(MRSA)的达托霉素MIC分布计算累积反应分数(CFR)。结果:ECMO与非ECMO组患者静滴达托霉素500 mg qd后,C_(max)分别为(85.5±25.4)μg/mL和(79.4±29.2)μg/mL,AUC_(max)分别为(674.2±267.2) mg·L^(-1)·h和(952.9±304.5) mg·L^(-1)·h,t_(1/2)分别为(10.9±2.1) h和(11.6±4.3) h,V_(d)为(0.21±0.12) L/kg和(0.150±0.061) L/kg, CL为(13.3±4.7) mL·h^(-1)·kg^(-1)和(9.2±3.4) mL·h^(-1)·kg^(-1),AUC_(max)和CL在两组间存在显著性差异,增加其余各药动学参数无显著性差异。蒙特卡洛模拟结果表明,当MRSA对达托霉素敏感性下降时(MIC≥1 mg/L),ECMO组PTA值和CFR值均小于90%。结论:体外膜肺氧合装置会在一定程度上影响达托霉素于重症感染患者体内的药代动力学特征。对于绝大多数行ECMO重症患者来说,当MIC≥1 mg/mL时,标准给药剂量的达托霉素无法有效覆盖MRSA所致感染,需要增加给药剂量以保证达托霉素CFR>90%。另外,建议此类患者实施达托霉素的治疗药物浓度监测,同时临床上应根据MRSA病原菌对药物的敏感性调整给药方案结论。
AIM: To investigate the effect of extracorporeal membrane oxygenation(ECMO) on the pharmacokinetics/pharmacodynamics(PK/PD) of daptomycin in critically ill patients. METHODS: Twenty four patients with severe infection in our hospital were randomly selected and divided into ECMO group and non ECMO group. They were intravenously injected with daptomycin 500 mg qd. After the drug reached the stability statement, venous blood was collected at different time points before and after the infusion. The plasma drug concentration was measured and the pharmacokinetic parameters were calculated. The probability target acquisition(PTA) and the cumulative fraction response(CFR) were calculated by Monte Carlo simulation. RESULTS: After dosing, the main pharmacokinetic parameters in ECMO and non-ECMO group were calculated and listed as follows: C_(max)were(85.5±25.4) μg/mL and(79.4±29.2) μg/mL, AUC_(max)were(674.2±267.2) mg·L^(-1)·h and(952.9±304.5) mg·L^(-1)·h, t_(1/2)were(10.9±2.1) h and(11.6±4.3) h, V_(d) were(0.21±0.12) L/kg and(0.150±0.061) L/kg, CL were(13.3±4.7) mL·h^(-1)·kg^(-1)and(9.2±3.4) mL·h^(-1)·kg^(-1). There were significant differences in AUC_(max)and CL between the two groups, and there was no significant difference in other pharmacokinetic parameters. Monte Carlo simulation results showed that when the sensitivity of MRSA to daptomycin decreased(MIC≥1 mg/L), the PTA values of ECMO group, non-ECMO group and healthy volunteers were less than 90%. CONCLUSION: ECMO may affect the PK/PD of daptomycin in patients with severe infection to a certain extent. When MIC≥1 mg/L, it is recommended to increase the dosage to achieve the expected antibacterial effect. In view of the individual differences of daptomycin in patients with ECMO, therapeutic drug monitoring(TDM) should be implemented in these patients, and the administration scheme should be adjusted according to the sensitivity of MRSA pathogens to drugs.
作者
胡琳璘
徐思露
厉伟兰
何杰
张锦璐
邵华
HU Linlin;XU Silu;LI Weilan;HE Jie;ZHANG Jinglu;SHAO Hua(Office of Clinical Trial Institution,Nanjing Zhongda Hospital,Southeast University,School of Medicine,Nanjing 210009,Jiangsu,China;Department of Pharmacy,Nanjing Zhongda Hospital,Southeast University,School of Medicine,Nanjing 210009,Jiangsu,China;Department of Pharmacy,Jiangsu Cancer Hospital,Jiangsu Institute of Cancer Research,The Affiliated Cancer Hospital of Nanjing Medical University,Nanjing 210009,Jiangsu,China;School of Medicine,Southeast University,Nanjing 210009,Jiangsu,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2022年第1期39-46,共8页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金(81503340)
南京药学会-常州四药医院药学科研基金(2019YX012)
江苏省药学会-奥赛康科研基金(A201904)。
