Population Pharmacokinetic-Pharmacodynamic Target Attainment Analysis of Flomoxef in the Serum and Liver Tissue of Patients Undergoing Hepatic Resection-Reference-Cited by-同舟云学术

Population Pharmacokinetic-Pharmacodynamic Target Attainment Analysis of Flomoxef in the Serum and Liver Tissue of Patients Undergoing Hepatic Resection

Published:2022-04-19 Issue:4 Volume:66 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Komatsu Toshiaki¹^ORCID,Tsumuraya Satomi²,Takayama Yoko³,Kaizu Takashi⁴,Okamoto Mikiko⁴,Tajima Hiroshi⁴,Nishizawa Nobuyuki⁴,Kubo Hidefumi⁴,Kumamoto Yusuke⁴,Okamoto Hirotsugu⁵,Hanaki Hideaki⁶,Atsuda Koichiro²

Affiliation:

1. Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan

2. Pharmacy Practice and Science I, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Kanagawa, Japan

3. Department of Infection Control and Infectious Diseases, Research and Development, Kitasato University School of Medicine, Sagamihara, Japan

4. Department of General-Pediatric-Hepatobiliary Pancreatic Surgery, Kitasato University School of Medicine, Sagamihara, Japan

5. Department of Anesthesiology, Kitasato University School of Medicine, Kanagawa, Japan

6. Infection Control Research Center, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan

Abstract

The purpose of this study was to investigate the population pharmacokinetics of prophylactic flomoxef based on serum and liver tissue concentrations and to demonstrate a pharmacodynamic target concentration in the serum and liver tissue exceeding the MIC in order to design an effective dosing regimen. Serum samples ( n = 210) and liver tissue samples ( n = 29) from 43 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index target value was regarded as the probability of maintaining flomoxef serum trough and liver tissue concentrations exceeding the MIC 90 values, 0.5 mg/L and 1.0 mg/L, for Escherichia coli and methicillin-susceptible Staphylococcus aureus , respectively. The final population pharmacokinetic model was a two-compartment model with linear elimination.

Funder

JSPS KAKENHI

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/aac.02303-21

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