Jang Soo Min, Yessayan Lenar, Dean Michael, Costello Gabrielle, Katwaru Ravi, Mueller Bruce A
Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, CA 92350, USA.
Department of Medicine Division of Nephrology, Michigan Medicine, Ann Arbor, MI 48109, USA.
Antibiotics (Basel). 2021 Sep 29;10(10):1184. doi: 10.3390/antibiotics10101184.
(1) Purpose of this study: determination of adsorption and transmembrane clearances (CL) of imipenem and relebactam in ex vivo continuous hemofiltration (CH) and continuous hemodialysis (CHD) models. These clearances were incorporated into a Monte Carlo Simulation (MCS), to develop drug dosing recommendations for critically ill patients requiring continuous renal replacement therapy (CRRT); (2) Methods: A validated ex vivo bovine blood CH and CHD model using two hemodiafilters. Imipenem/relebactam and urea CL at different ultrafiltrate/dialysate flow rates were evaluated in both CH and CHD. MCS was performed to determine dose recommendations for patients receiving CRRT; (3) Results: Neither imipenem nor relebactam adsorbed to the CRRT apparatus. The CL of imipenem, relebactam, and urea approximated the effluent rates (ultrafiltrate/dialysate flow rates). The types of hemodiafilter and effluent rates did not influence CL except in a dialysis flow rate of 1 L/h and 6 L/h in the CHD with relebactam ( < 0.05). Imipenem and relebactam 200 mg/100 mg every 6 h were sufficient to meet the standard time above the MIC pharmacodynamic targets in the modeled CRRT regimen of 25 kg/mL/h. (4) Conclusions: Imipenem and relebactam are not removed by adsorption to the CRRT apparatus, but readily cross the hemodiafilter membrane in CH and CHD. Dosage adjustment of imipenem/relebactam is likely required for critically ill patients receiving CRRT.
(1) 本研究目的：在体外持续血液滤过（CH）和持续血液透析（CHD）模型中测定亚胺培南和瑞来巴坦的吸附及跨膜清除率（CL）。将这些清除率纳入蒙特卡洛模拟（MCS），以制定针对需要持续肾脏替代治疗（CRRT）的危重症患者的给药建议；(2) 方法：使用两种血液透析滤过器建立经过验证的体外牛血CH和CHD模型。在CH和CHD中评估不同超滤/透析液流速下亚胺培南/瑞来巴坦和尿素的CL。进行MCS以确定接受CRRT患者的剂量建议；(3) 结果：亚胺培南和瑞来巴坦均未吸附到CRRT装置上。亚胺培南、瑞来巴坦和尿素的CL接近流出速率（超滤/透析液流速）。除了在瑞来巴坦的CHD中透析流速为1 L/h和6 L/h时（<0.05），血液透析滤过器类型和流出速率不影响CL。在25 kg/mL/h的模拟CRRT方案中，每6小时给予亚胺培南200 mg/瑞来巴坦100 mg足以达到高于MIC药效学目标的标准时间。(4) 结论：亚胺培南和瑞来巴坦不会因吸附到CRRT装置而被清除，但在CH和CHD中很容易穿过血液透析滤过器膜。接受CRRT的危重症患者可能需要调整亚胺培南/瑞来巴坦的剂量。
