title: Pharmacokinetic-pharmacodynamic target attainment analysis of cefozopran in Japanese adult patients.
abstract: This study aimed to perform a pharmacokinetic-pharmacodynamic (PK-PD) target attainment analysis to create a dosing strategy for cefozopran in Japanese adult patients. A total of 145 plasma concentration samples from 32 adult patients were used for a population pharmacokinetic modeling and Monte Carlo simulation to assess the probability of attaining the PK-PD target (70% of the time above the minimum inhibitory concentration for the bacterium). The final population pharmacokinetic model was based on a two-compartment model, and creatinine clearance (Cl(cr)) and body weight (BW) were the most significant covariates: Cl(l/h) = 0.0263 x Cl(cr) + 1.49, V (c)(l) = 0.185 x BW(0.931), Q(l/h) = 4.55, V (p)(l) = 5.86, where Cl is the clearance, V (c) is the volume of distribution of the central compartment, Q is the intercompartmental clearance, and V (p) is the volume of distribution of the peripheral compartment. The Monte Carlo simulation demonstrated that 1 g q 12 h achieved a PK-PD target attainment probability of > or =85% against Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae isolates. However, against Haemophilus influenzae and Pseudomonas aeruginosa isolates, 1 g q 8 h and (2 g, 1 g, 1 g) q 8 h were required to achieve a high probability, which value varied with the Cl(cr) and BW of the patient. These results provide a PK-PD-based strategy for tailoring cefozopran regimens in Japanese adult patients.
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: Kenichi
authors.initials: K
authors.lastname: Nomura
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
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007813:Laparotomy / Q000009:adverse effects; D008297:Male; D008826:Microbial Sensitivity Tests / Q000592:standards; D008875:Middle Aged; D009010:Monte Carlo Method; D009503:Neutropenia / Q000150:complications; D000097586:Cefozopran
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097586:Cefozopran