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Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation

 Soyoung Kang  ;  June Young Jang  ;  Jongsung Hahn  ;  Dasohm Kim  ;  Jun Yeong Lee  ;  Kyoung Lok Min  ;  Seungwon Yang  ;  Jin Wi  ;  Min Jung Chang 
 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol.64(5) : e00249-20, 2020-05 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents / administration & dosage ; Anti-Bacterial Agents / pharmacokinetics* ; Anti-Bacterial Agents / therapeutic use ; Bacteria / drug effects ; Cephalosporins / administration & dosage ; Cephalosporins / pharmacokinetics* ; Cephalosporins / therapeutic use ; Continuous Renal Replacement Therapy / statistics & numerical data ; Drug Dosage Calculations* ; Extracorporeal Membrane Oxygenation / statistics & numerical data* ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged
ECMO ; beta-lactams ; cephalosporin ; pharmacodynamics ; population pharmacokinetics
To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution. Cefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2 g every 8 h for intravenous bolus injection or 2 g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO. We established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Wi, Jin(위진) ORCID logo https://orcid.org/0000-0003-0655-5130
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