Article ID Journal Published Year Pages File Type
3348082 Diagnostic Microbiology and Infectious Disease 2008 6 Pages PDF
Abstract

This study aimed to assess the peritoneal pharmacodynamics of intravenous doripenem using population pharmacokinetic modeling and Monte Carlo simulation. Drug concentrations in peritoneal fluid (PF) and serum from 11 laparotomy patients and MIC distributions against clinical isolates in Japan for 4 Gram-negative organisms were used. The probabilities of attaining the pharmacodynamic target (40% T > MIC) were greater in PF than in serum. To achieve a ≥90% probability of target attainment in PF, 0.25 g tid and 0.5 g tid (0.5-h infusions) had to be sufficient against Escherichia coli, Klebsiella spp., and Enterobacter cloacae; however, 1 g tid (0.5-h infusion) was required against Pseudomonas aeruginosa. Prolonged (4-h) infusion regimens resulted in increase of the target attainment probabilities in PF for P. aeruginosa. These results should help to achieve a better understanding of the peritoneal pharmacodynamics of doripenem while also helping to rationalize and optimize the dosing regimen for intra-abdominal infections.

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