Pharmacokinetic changes of meropenem in sepsis patients: A Comparative Review

Abstract: Background: Sepsis is a life-threatening organ dysfunction occurring during infections. Meropenem is a hydrophilic β-lactam carbapenem antibiotic. Its pharmacokinetic parameters are expected to change due to sepsis-induced physiological alterations and will thus require altered dosing strategies for optimal treatment of sepsis patients. Aim: This is a review with the purpose to compare the pharmacokinetics of meropenem between healthy adults and adult septic patients and explore the potential covariates that affect the pharmacokinetic parameters. Methods: Articles that were explored were collected from PubMed and were screened through inclusion and exclusion criteria. Results: Total of 19 articles were identified and selected. Participants in the studies were in the age range of 18–91 years, with the weight range of 37–120 kg. Volume of distribution at steady-state in the healthy participants had a median of 22.2 L, while the volume of distribution in septic patients had median 27.6 L. Clearance had median 13.89 L/h in healthy, compared to the median 10.43 L/h in septic. The median half-life was 1 h in healthy, whereas in septic, the median half-life was 2.5 h. Patients with fluid overload from fluid therapy had larger Vd & lower Cl, while patients with creatinine clearance < 50 mL/min had lower Cl. Conclusions: The physiological alterations developing in sepsis lead to an increase of the meropenem’s distribution and a decrease of its elimination, which is exacerbated by fluid overload. These findings could be a good starting point for building a physiologically based pharmacokinetic model of meropenem in sepsis.