| Autor: |
Toshiaki Komatsu, Satomi Tsumuraya, Yoko Takayama, Takashi Kaizu, Mikiko Okamoto, Hiroshi Tajima, Nobuyuki Nishizawa, Hidefumi Kubo, Yusuke Kumamoto, Hirotsugu Okamoto, Hideaki Hanaki, Koichiro Atsuda |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Antimicrob Agents Chemother |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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