Microdialysis study of imipenem distribution in the intraperitoneal fluid of rats with or without experimental peritonitis.
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.
Lefeuvre
Sandrine
S
EA 3809, Pôle Biologie Santé (PBS), Médecine-Sud, Niveau 1, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France.
Marchand
Sandrine
S
Lamarche
Isabelle
I
Mimoz
Olivier
O
Couet
William
W
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D045604:Extracellular Fluid / Q000378:metabolism*; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism*; D017551:Microdialysis; D010538:Peritonitis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D015378:Imipenem