title: Peritoneal penetration and pharmacodynamic exposure of intravenous cefozopran in abdominal surgery patients.
abstract: This study aimed to examine the peritoneal penetration and pharmacodynamic exposure of intravenous cefozopran. Cefozopran 1 g was administered to 10 patients before abdominal surgery. Venous blood and peritoneal fluid (PF) samples were obtained at the end of the 0.5-h infusion and at 1, 2, 3, 4, 5 and 6 h thereafter. Drug concentrations in plasma and PF were determined, analysed pharmacokinetically and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. Cefozopran penetrated well into PF, with a mean (+/-standard deviation) maximum drug concentration in PF/plasma ratio of 0.65+/-0.17 (n=10) and area under the concentration-time curve ratio of 0.92+/-0.13. The probabilities of attaining the pharmacodynamic exposure target (PTA), defined as 70% of the time above the MIC, in PF were almost identical to those in plasma. The PTAs were 95-100% against Escherichia coli, Enterobacter spp. and Staphylococcus aureus with 0.5 g every 12 h; however, 1 g every 8 h or 1 g every 6 h was required for 93-98% PTA against Pseudomonas aeruginosa. These results should help us to understand the peritoneal pharmacokinetics of cefozopran whilst also helping to choose the appropriate dosage for surgical intra-abdominal infections.
authors.affiliation: Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 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: Shusaku
authors.initials: S
authors.lastname: Matsuda
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohge
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takesue
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001202:Ascitic Fluid / Q000737:chemistry*; D001774:Blood Chemical Analysis; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D003198:Computer Simulation; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013997:Time Factors; D014018:Tissue Distribution; D000097586:Cefozopran
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097586:Cefozopran