title: Penetration into and exposure of cefozopran in pelvic retroperitoneal space exudate.
abstract: This study aimed to examine the penetration into and exposure of cefozopran in the pelvic retroperitoneal space exudate of patients undergoing radical hysterectomy and pelvic lymphadenectomy. Cefozopran (1 g) was administered by 1-h infusion after the end of surgery, and venous blood and exudate samples were obtained 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 8 h thereafter. Drug concentrations in serum and the exudate were determined by a bioassay, analyzed pharmacokinetically, and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. The exudate/serum ratio of the area under the drug concentration-time curve was 0.76 +/- 0.19 (mean +/- SD), and the simulated concentrations were higher in the exudate than in serum after 2.4 h post-dose. The probability of attaining the pharmacodynamic exposure target (70% of the time above the MIC; i.e., probability of target attainment; PTA) was 94.9% and 100%, respectively, against Escherichia coli and Klebsiella species with 1 g every 12 h; however, 1 g every 8 h was required for a PTA value of 90% or more at an MIC of 8 microg/ml. We consider that these results will help clinicians to better understand the penetration into and exposure of cefozopran in the female genital cavity, while also helping to rationalize the dosage of this agent for gynecological-surgery infections.
authors.affiliation: Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, 734-8551, Japan. ikawak@hiroshima-u.ac.jp
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Tamaya
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005122:Exudates and Transudates / Q000378:metabolism*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008197:Lymph Node Excision; D008826:Microbial Sensitivity Tests / Q000592:standards; D008875:Middle Aged; D009010:Monte Carlo Method; D010388:Pelvis; D011183:Postoperative Complications / Q000188:drug therapy / Q000382:microbiology; D012187:Retroperitoneal Space; D000097586:Cefozopran
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097586:Cefozopran