In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 4 ( 2022-04-19)
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. Creatinine clearance (CL CR ) was identified as a significant covariate influencing total clearance when CL CR was less than 60 mL/min. The probability of achieving concentrations in the serum and liver tissue exceeding the MIC 90 for E. coli or methicillin-susceptible S. aureus for a 1 g bolus dose was above 90% at 2 h after the initial dose. Our findings suggest that population pharmacokinetic parameters are helpful for evaluating flomoxef pharmacokinetics and determining intraoperative flomoxef redosing intervals.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/aac.02303-21
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2022
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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