# Population pharmacokinetics of imipenem in different populations for individualized dosing: a systematic review

## TL;DR

This paper reviews how imipenem's drug levels vary in different patients and identifies factors like kidney function and weight that affect dosing.

## Contribution

The study systematically integrates population pharmacokinetic models of imipenem and highlights key covariates for individualized dosing.

## Key findings

- Imipenem pharmacokinetics are best modeled using two-compartment models.
- Renal function and body weight are key factors influencing imipenem clearance and distribution.
- External validation of models is limited, highlighting a research gap.

## Abstract

Imipenem is a broad-spectrum carbapenem antibiotic for severe infections with significant pharmacokinetic (PK) variability. This review systematically synthesized published population pharmacokinetic (popPK) studies to identify key covariates and guide individualized dosing for patients with various conditions.

A systematic PubMed and Web of Science search identified imipenem popPK models. Studies employing nonlinear mixed-effects modeling in patients with various conditions were included, and data were extracted independently by two reviewers via a standardized form. The study characteristics and PK parameter estimates were compared.

This systematic review of 18 popPK studies revealed that imipenem PKs were predominantly characterized by two-compartment models. The clearance of imipenem varied from 4.79 to 16.2 L/h in adults. Creatinine clearance (CLcr) was the most consistent and significant covariate for imipenem clearance, whereas body weight (BW) was frequently identified for volume of distribution. Other clinically relevant covariates, including the glomerular filtration rate (GFR), age, and serum ALB level, were also incorporated into the final models for specific patient subpopulations. All models applied internal validations, such as bootstrap and visual predicative check, but only three studies performed external validation.

This review systematically integrates existing popPK models of imipenem, highlighting renal function and BW as key covariates. This study provides valuable insights for individualized dosing while identifying critical research gaps, particularly the need for external validation and focused studies in special populations.