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: Kazuro Ikawa, Kenichi Nomura, Norifumi Morikawa, Kayo Ikeda, Hiroki Ohge, Taijiro Sueda, Masafumi Taniwaki
• Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (J Infect Chemother) Vol. 14 Issue 2 Pg. 130-6 (Apr 2008) ISSN: 1341-321X [Print] Netherlands
• PMID: 18622676 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Cephalosporins

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Bacteria (drug effects)
• Bacterial Infections (drug therapy, microbiology)
• Cephalosporins (administration & dosage, pharmacokinetics, therapeutic use)
• Female
• Humans
• Laparotomy (adverse effects)
• Male
• Microbial Sensitivity Tests (standards)
• Middle Aged
• Monte Carlo Method
• Neutropenia (complications)
• Cefozopran