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Updated: Aug 5, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

Imipenem and relebactam pharmacokinetics in peritoneal fluid: microdialysis reveals infection-independent penetration

Huan Tong1, Zekun Cao1,2, Jiakai Li1,2

  • 1Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs, Department of Pharmacy, The Third Hospital of Changsha, Changsha, People's Republic of China.

Antimicrobial Agents and Chemotherapy
|July 31, 2026
PubMed

Insights

Imipenem/relebactam shows limited peritoneal penetration for treating resistant infections. Relebactam achieved higher concentrations than imipenem in peritoneal fluid, but overall exposure may be insufficient for efficacy.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Drug Development

Background:

  • Carbapenem-resistant Enterobacterales (CRE) pose a significant threat in complicated intra-abdominal infections.
  • Imipenem/relebactam is a potential treatment for CRE infections, but its efficacy depends on adequate tissue drug concentrations.
  • Limited data exist on the pharmacokinetic penetration of imipenem/relebactam into peritoneal tissue.

Purpose of the Study:

  • To evaluate the peritoneal fluid penetration of imipenem and relebactam in a rat model.
  • To compare drug concentrations in peritoneal fluid versus plasma.
  • To assess the impact of infection on drug distribution and permeability.

Main Methods:

  • Microdialysis was used to dynamically monitor unbound imipenem and relebactam concentrations in plasma and peritoneal fluid of healthy and infected rats.
  • Pharmacokinetic parameters were determined using non-compartmental and two-compartment modeling.
  • Pharmacodynamic target attainment (PTA) was analyzed based on EUCAST criteria.

Main Results:

  • Imipenem showed low peritoneal fluid exposure (fluid/plasma AUC ratios of ~0.27-0.29).
  • Relebactam demonstrated high peritoneal fluid penetration (fluid/plasma AUC ratios of ~0.81-0.86), with concentrations nearly equivalent to plasma.
  • Infection altered relebactam's distribution volume and clearance but not peritoneal permeability; PTA analysis indicated a reduced probability of achieving target concentrations at an MIC of 1 mg/L.

Conclusions:

  • Relebactam penetrates the peritoneal cavity effectively, while imipenem penetration is limited.
  • Current dosing strategies may not ensure adequate peritoneal drug concentrations for imipenem/relebactam to be effective against CRE infections.
  • Further research into optimized dosing regimens is warranted to improve therapeutic outcomes.
Keywords:
imipenemintraperitoneal infectionmicrodialysispharmacokineticsrelebactam

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