1. Does Two-Step Infusion Improve the Pharmacokinetics/Pharmacodynamics Target Attainment of Meropenem in Critically Ill Patients?
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Chen, Jiaojiao, Wang, Quanfang, Li, Sihan, Han, Ruiying, Wang, Chuhui, Cheng, Shiqi, Yang, Baogui, Diao, Lizhuo, Yang, Tingting, Sun, Dan, Zhang, Di, Dong, Yalin, and Wang, Taotao
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INFUSION therapy , *CRITICALLY ill , *PHARMACOKINETICS , *MEROPENEM , *PHARMACODYNAMICS - Abstract
• A PBPK model of meropenem for critically ill patients was established. • The % f T>MIC values varied greatly in different two-step infusion (TIT) strategies. • The TIT did not improve the PK/PD target attainment rate of meropenem. • Intermittent infusion was appropriate at MICs of ≤1 mg/L. • Prolonged infusion was recommended at MICs of 2–8 mg/L. The optimal method for administering meropenem remains controversial. This study was conducted to explore the optimal two-step infusion strategy (TIT), and to investigate whether TIT is superior to intermittent infusion therapy (IIT) and prolonged infusion therapy (PIT). A physiologically based pharmacokinetics model for critically ill patients was established and evaluated. The validated model was utilized to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) target attainment of meropenem. The PK/PD target attainment of different TITs varied greatly, and the total infusion duration and the first-step dose greatly affected these values. The optimal TIT was 0.25 g (30 min) + 0.75 g (150 min) at MICs of ≤2 mg/L, and 0.25 g (45 min) + 0.75 g (255 min) at MICs of 4–8 mg/L. The PK/PD target attainment of optimal TIT, PIT, and IIT were 100 % at MICs of ≤1 mg/L. When MIC increased to 2–8 mg/L, the PK/PD target attainment of optimal TIT was similar to that of PIT and higher than IIT. In conclusion, TIT did not significantly improve the PK/PD target attainment of meropenem compared with PIT. IIT is adequate at MICs of ≤1 mg/L, and PIT may be the optimal meropenem infusion method in critically ill patients with MICs of 2–8 mg/L. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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