Original Research
Sunday, November 12, 2023
12:45 PM–02:15 PM
Abstract
Introduction:
Once daily intravenous cefepime dosing is generally recommended in patients with kidney failure (KF) receiving intermittent hemodialysis (IHD) but requires hospitalization or daily clinic visits. Post-dialytic administration with a higher cefepime dose can offer an alternative treatment option for some patients who are managed in an outpatient dialysis center. However, limited pharmacokinetic data exists regarding post-dialytic cefepime dosing in these patients.
Research Question or Hypothesis:
This study was performed to predict efficacy and safety of post-dialytic cefepime dosing in patients with KF receiving thrice-weekly IHD compared with daily dosing.
Study Design:
In-silico study using Monte Carlo simulation (MCS)
Methods:
One-compartment pharmacokinetic models were developed using pertinent demographic and pharmacokinetic data to generate cefepime plasma concentrations in anuric patients with KF receiving 4-hour IHD thrice-weekly (Mon-Wed-Fri) at dialysate rate 800 mL/min. MCS was performed to compare the probability of target attainment (PTA) of cefepime 2g post-dialytic and 1g daily dosing regimens in a 5,000 virtual cohort for one week. The pharmacodynamic target was 60% free plasma concentrations above the minimum inhibitory concentration (60%fT>MIC; MIC=8 mg/L for Pseudomonas aeruginosa) with PTA>90% being optimal for efficacy. For safety, the pre-dialysis plasma concentrations were evaluated using the suggested neurotoxicity threshold of 20 mg/L.
Results:
For efficacy, cefepime 2g post-dialytic dosing attained PTA>90% everyday but the last of a 3-day interdialytic period (ie. PTA 65.9% on Sunday) while 1g daily dosing attained PTA>90% on each of all simulated days. For safety, 2g post-dialytic and 1g daily dosing regimens elevated pre-dialysis concentrations above the threshold in up to 71% and 100% of a 5,000 virtual cohort.
Conclusion:
Cefepime 2g post-dialytic dosing is likely suboptimal for a 3-day interdialytic period. For safety, while potential toxicity risk is higher with 1g daily dosing, both dosing regimens pose significant neurotoxicity risk in most KF patients receiving thrice-weekly IHD. Clinical studies are warranted to validate these MCS findings.
Presenting Author
Susan Lewis PharmDUniversity of Findlay College of Pharmacy
Authors
Olivia Caiazza PharmD candidate
University of Findlay College of Pharmacy
Olivia Pauly PharmD candidate
University of Findlay College of Pharmacy
Nerissa Wan PharmD candidate
University of Findlay College of Pharmacy