title: Penetration and exposure of cefotiam into the peritoneal fluid of abdominal surgery patients after intravenous administration.
abstract: The present study aimed to examine the peritoneal pharmacokinetics and pharmacodynamic exposure of intravenous cefotiam. One gram of cefotiam was administered to eight patients before abdominal surgery. Venous blood and peritoneal fluid (PF) samples were obtained at the end of infusion (0.5 h) and 1, 2, 3, 4, 5, and 6 h afterwards. The drug concentrations in the plasma and PF were determined, analyzed pharmacokinetically, and used for a stochastic simulation with minimum inhibitory concentration (MIC) data. Cefotiam penetrated well into the PF with the area under the drug concentration-time curve ratio of 0.88 +/- 0.18 (mean +/- SD, n = 8). Regarding the pharmacodynamic exposures against Escherichia coli and Klebsiella species, the probabilities of attaining the bacteriostatic target (40% of the time above MIC) in the PF using 0.5 g every 12 h, 1 g every 12 h, and 2 g every 12 h were 88.3-93.6%. However, 1 g every 8 h was needed for 89.7 and 91.6% probabilities of attaining the bactericidal target (70% of the time above MIC). These results should help us to understand better the peritoneal pharmacokinetics of cefotiam while also helping us to choose the appropriate dosage for intra-abdominal infections.
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Japan. ikawak@hiroshima-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Ikawa
authors.forename: N
authors.initials: N
authors.lastname: Morikawa
authors.forename: K
authors.initials: K
authors.lastname: Fukuhara
authors.forename: S
authors.initials: S
authors.lastname: Hayato
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Soga
authors.forename: H
authors.initials: H
authors.lastname: Ohge
authors.forename: T
authors.initials: T
authors.lastname: Sueda
mesh_terms: D034841:Abdominal Cavity / Q000382:microbiology / Q000601:surgery; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001202:Ascitic Fluid / Q000378:metabolism*; D001424:Bacterial Infections / Q000188:drug therapy*; D015310:Cefotiam / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007709:Klebsiella / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D011446:Prospective Studies; D013530:Surgical Wound Infection / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D015310:Cefotiam