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Published on: July 20, 2022
Microdialysis study of imipenem distribution in the intraperitoneal fluid of rats with or without experimental
Sandrine Lefeuvre1, Sandrine Marchand, Isabelle Lamarche
1EA 3809, Pôle Biologie Santé (PBS), Médecine-Sud, Niveau 1, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France.
Abstract:
The purpose of this study was to extend the use of microdialysis to the investigation of antibiotic distribution into the intraperitoneal fluid of rats with or without peritonitis. Microdialysis probes were inserted into the jugular vein and peritoneal cavity of control rats or rats with intra-abdominal sepsis (n = 8 in each group) induced by cecal ligation and punctures. Imipenem (IPM) probe recoveries were determined in each rat by retrodialysis by drug. IPM was infused intravenously at a dose of 30 mg . kg(-1) over 30 min, microdialysis samples were collected for 120 min, and IPM concentrations were determined by high-performance liquid chromatography. Intraperitoneal infection had no statistically significant effect on IPM clearance (11.9 +/- 2.3 ml.min(-1).kg(-1) in control rats versus 10.9 +/- 2.1 ml.min(-1).kg(-1) in rats with peritonitis) or the volume of distribution (296 +/- 47 ml.kg(-1) in control rats versus 310 +/- 49 ml.kg(-1) in rats with peritonitis). IPM concentration profiles in intraperitoneal fluid and blood were virtually superimposed in control rats, whereas in infected animals, the mean intraperitoneal IPM concentrations were apparently slightly lower than corresponding blood levels. However, the areas under the concentration-versus-time curve estimated in intraperitoneal fluid and blood were not significantly different in both groups, with the corresponding ratios close to unity (1.01 +/- 0.19 and 0.89 +/- 0.28 in control rats and rats with peritonitis, respectively). In conclusion, IPM distribution in intraperitoneal fluid is rapid and complete both in control rats and in rats with peritonitis.
Insights
This study shows imipenem distributes rapidly and completely into peritoneal fluid, even during peritonitis. Antibiotic levels in peritoneal fluid closely match blood concentrations in rats.
Area of Science:
- Pharmacokinetics
- Infectious Diseases
- Surgical Research
Background:
- Understanding antibiotic distribution is crucial for effective treatment of intra-abdominal infections.
- Peritonitis can alter drug pharmacokinetics, potentially impacting therapeutic efficacy.
Purpose of the Study:
- To investigate the distribution of imipenem (IPM) into peritoneal fluid using microdialysis in rats.
- To assess the impact of peritonitis on IPM distribution and its pharmacokinetic parameters.
Main Methods:
- Microdialysis probes were used to measure IPM concentrations in jugular vein blood and peritoneal fluid in control rats and rats with induced peritonitis.
- Imipenem was administered intravenously, and samples were collected over 120 minutes.
- High-performance liquid chromatography was used for IPM quantification.
Main Results:
- Peritonitis did not significantly affect IPM clearance or volume of distribution.
- IPM concentrations in peritoneal fluid closely mirrored those in blood in both control and peritonitis groups.
- Area under the concentration-time curve ratios between peritoneal fluid and blood were near unity.
Conclusions:
- Imipenem demonstrates rapid and complete distribution into the peritoneal fluid.
- Peritonitis does not significantly impede imipenem distribution into the peritoneal cavity.
- Microdialysis is a viable method for studying antibiotic distribution in peritoneal fluid.