Optimization of meropenem continuous infusion based on Monte Carlo simulation integrating with degradation study

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Drug Stability and Formulation
• Infectious Diseases and Antimicrobial Therapy

Background:

• Meropenem degradation challenges continuous infusion (CI) implementation.
• Limited data exists on meropenem degradation's impact on probability of target attainment (PTA).
• Evaluating meropenem brand stability and degradation consequences on PTA is crucial for optimizing therapy.

Purpose of the Study:

• To assess the in-bottle stability of various meropenem brands under different environmental conditions.
• To determine the impact of meropenem degradation on PTA in simulated clinical scenarios.
• To evaluate the feasibility of meropenem CI for achieving therapeutic targets.

Main Methods:

• Seven meropenem generic brands were tested at varying concentrations and temperatures (25-37°C) for 8 hours.
• A linear mixed-effects model analyzed degradation rates.
• In-bottle stability data informed pharmacokinetic simulations using a population model for critical illness.

Main Results:

• Meropenem stability was influenced by time, temperature, and concentration, but degradation differences between generics were minor.
• Eight-hour meropenem CI achieved higher PTA than 3-hour infusions, even under high degradation.
• Degradation had minimal impact on PTA, though dose adjustments (1.5-2g q8h) restored targets in specific patient groups.

Conclusions:

• Meropenem CI with 8-hour renewal infusions is a feasible strategy to maximize efficacy, even in tropical climates.
• This approach is effective against difficult-to-treat pathogens.
• Considering drug stability is vital for successful meropenem CI implementation.