Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling

被引:3
作者
Kang, Soyoung [1 ,2 ,3 ]
Yang, Seungwon [2 ,3 ,4 ,5 ]
Hahn, Jongsung [2 ,3 ,6 ]
Jang, June Young [1 ]
Min, Kyoung Lok [1 ]
Wi, Jin [7 ,8 ]
Chang, Min Jung [1 ,2 ,3 ,9 ]
机构
[1] Yonsei Univ, Dept Pharmaceut Med & Regulatory Sci, Incheon 21983, South Korea
[2] Yonsei Univ, Dept Pharm, Incheon 21983, South Korea
[3] Yonsei Univ, Yonsei Inst Pharmaceut Sci, Incheon 21983, South Korea
[4] Kyung Hee Univ, Coll Pharm, Dept Pharm, Seoul 02447, South Korea
[5] Kyung Hee Univ, Coll Pharm, Grad Sch, Dept Regulatory Sci, Seoul 02447, South Korea
[6] Jeonbuk Natl Univ, Sch Pharm, Jeonju 54896, South Korea
[7] Gachon Univ, Dept Internal Med, Div Cardiol, Gil Med Ctr, Incheon 21565, South Korea
[8] Yonsei Univ, Dept Internal Med, Div Cardiol, Coll Med, Seoul 03722, South Korea
[9] Yonsei Univ, Grad Program Ind Pharmaceut Sci, Incheon 21983, South Korea
基金
新加坡国家研究基金会;
关键词
meropenem; extracorporeal membrane oxygenation; ECMO; dosage optimization; population pharmacokinetics; CONTINUOUS-INFUSION; PHARMACOKINETIC CHANGES; CARDIOGENIC-SHOCK; PK/PD INDEXES; LIFE-SUPPORT; STABILITY; ADULTS; PHARMACODYNAMICS; ANTIBIOTICS; THERAPY;
D O I
10.3390/jcm11226621
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Our objective was to determine an optimal dosage regimen of meropenem in patients receiving veno-arterial extracorporeal membrane oxygenation (V-A ECMO) by developing a pharmacokinetic/pharmacodynamic (PK/PD) model. Methods: This was a prospective cohort study. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF). The population pharmacokinetic model was developed using nonlinear mixed-effects modeling. A Monte Carlo simulation was used (n = 10,000) to assess the probability of target attainment. Results: Thirteen adult patients on ECMO receiving meropenem were included. Meropenem pharmacokinetics was best fitted by a two-compartment model. The final pharmacokinetic model was: CL (L/h) = 3.79 x 0.44(CRRT), central volume of distribution (L) = 2.4, peripheral volume of distribution (L) = 8.56, and intercompartmental clearance (L/h) = 21.3. According to the simulation results, if more aggressive treatment is needed (100% fT > MIC target), dose increment or extended infusion is recommended. Conclusions: We established a population pharmacokinetic model for meropenem in patients receiving V-A ECMO and revealed that it is not necessary to adjust the dosage depending on V-A ECMO. Instead, more aggressive treatment is needed than that of standard treatment, and higher dosage is required without continuous renal replacement therapy (CRRT). Also, extended infusion could lead to better target attainment, and we could provide updated nomograms of the meropenem dosage regimen.
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页数:11
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