Ertapenem clearance during modeled continuous renal replacement therapy.

Area of Science:

• Pharmacokinetics
• Nephrology
• Critical Care Medicine

Background:

• Continuous renal replacement therapy (CRRT) is crucial for managing critically ill patients with kidney injury.
• Antibiotic dosing in CRRT requires careful consideration due to altered drug clearance.
• Ertapenem is a carbapenem antibiotic with important clinical applications.

Purpose of the Study:

• To quantify ertapenem transmembrane clearance (CLtm) in vitro during CRRT.
• To compare ertapenem clearance using different hemodiafilter types and flow rates.
• To assess the impact of CRRT parameters on ertapenem sieving and saturation coefficients.

Main Methods:

• An in vitro model simulating continuous hemofiltration and hemodialysis was utilized.
• Ertapenem and urea clearance were measured across AN69 and polysulfone hemodiafilters.
• Experiments were conducted at varying dialysate and ultrafiltration rates (1-6 L/hour).

Main Results:

• Ertapenem and urea showed high sieving coefficients (SC) in hemofiltration, with no significant difference between filter types.
• In hemodialysis, ertapenem saturation coefficients (SA) and CLtm differed significantly between AN69 and polysulfone filters at high dialysate flow rates.
• AN69 filter SA decreased with increasing dialysate flow, while polysulfone filter SA remained consistent.

Conclusions:

• Ertapenem is substantially cleared in in vitro CRRT models.
• Observed ertapenem SC and SA in CRRT models may differ from published unbound fractions.
• In vivo validation is needed to confirm these findings and guide potential ertapenem dosage adjustments in CRRT patients.