(535) Impact of Various eGFR Equations on the Pharmacokinetics of Meropenem in Critically Ill Adults

Introduction: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill. This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance.

Methods: This single center study evaluated adults hospitalized in an ICU who received intravenous meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (N = 19) and an opportunistically sampled qualification cohort (N = 32). A non-linear mixed effects model was developed using parametric methods to estimate meropenem serum concentrations.

Results: The best fit structural model in the richly-sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70 kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best predicted meropenem clearance. The mean (standard error) Vd in the final model was 17.4 (3.07) L and clearance was 11.5 (1.55) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias.

Conclusions: Contemporary eGFR equations which use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared to creatinine only or cystatin C only eGFR equations in adult critically ill patients.