title: Pharmacodynamic assessment of doripenem in peritoneal fluid against Gram-negative organisms: use of population pharmacokinetic modeling and Monte Carlo simulation.
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 > or =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.
authors.affiliation: Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan. ikawak@hiroshima-u.ac.jp
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohge
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000328:Adult; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001202:Ascitic Fluid / Q000378:metabolism*; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D000077726:Doripenem; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D013530:Surgical Wound Infection / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem