(1) Purpose of this study: determination of adsorption and transmembrane clearances (CLTM) 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 CLTM 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 CLTM of
imipenem,
relebactam, and
urea approximated the effluent rates (ultrafiltrate/
dialysate flow rates). The types of hemodiafilter and effluent rates did not influence CLTM except in a dialysis flow rate of 1 L/h and 6 L/h in the CHD with
relebactam (p < 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.