Original Research
Sunday, October 13, 2024
12:45 PM–02:15 PM
Abstract
Introduction:
Optimal meropenem dosing for patients with kidney failure undergoing intermittent hemodialysis (IHD) is not well-defined. Daily dosing is typically recommended, but is inconvenient, necessitating hospitalization or daily clinical visit. Post-dialytic administration of higher meropenem doses offers a practical alternative, but lacks data. Monte Carlo Simulations (MCS) can evaluate the feasibility of post-dialytic dosing in an outpatient setting.
Research Question or Hypothesis:
Is post-dialytic meropenem dosing effective and safe for patients receiving thrice-weekly IHD compared with daily dosing?
Study Design:
A prospective in-silico study using MCS
Methods:
Relevant demographic and pharmacokinetic parameters were used to develop mathematical models predicting meropenem plasma concentrations in anuric kidney failure patients receiving 4-hour IHD thrice-weekly (Monday-Wednesday-Friday) at dialysate rate of 600 or 800mL/min for one-week. MCS assessed probability of target attainment (PTA) for doses including 250-1000mg daily and 500-2000mg post-dialytic dosing regimens in 5,000 virtual patients. Pharmacodynamic targets were 40%fT>MIC and 40%fT>MICx4 with an MIC of 2 mg/L assuming Pseudomonas aeruginosa infections. Doses attaining PTA=90% each day during one week were considered optimal. Potential neurotoxicity risk was evaluated using a toxicity threshold of >64 mg/mL at the end of each simulated day.
Results:
For the 40%fT>MIC target, meropenem 250-1000mg daily and 2000mg post-dialytic doses achieved a PTA~90% in virtual patients receiving thrice-weekly IHD at both dialysate rates over seven simulated days. Achieving the more aggressive target (40%fT>MICx4) required 500-1000mg daily doses. No tested post-dialytic dose reached this target, resulting in lower PTA on non-administration days. None of the simulated doses elevated the neurotoxicity risk.
Conclusion:
Post-dialytic meropenem 2000mg dose is likely effective and safe for patients undergoing thrice-weekly IHD. For achieving more aggressive targets, this post-dialytic dosing strategy may not be optimal, and daily dosing would be necessary to ensure these targets. Clinical studies are needed to validate these MCS findings.
Presenting Author
Susan Lewis PharmDUniversity of Findlay College of Pharmacy
Authors
Elizabeth Bockey PharmD (Anticipated 2026)
The University of Findlay
Madeline Deiderick PharmD (Anticipated 2026)
The University of Findlay
Jacob Holmes PharmD (Anticipated 2026)
The University of Findlay
Sydnee Payer PharmD (Anticipated 2026)
The University of Findlay
Sierra Shoemaker PharmD (Anticipated 2026)
The University of Findlay