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Population pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

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Author(s)
Dong-Hwan LeeYong Kyun KimKyubok JinMyoung Joo KangYoung-Don JooYang Wook KimYoung Soo MoonJae-Gook ShinSungmin Kiem
Keimyung Author(s)
Jin, Kyu Bok
Department
Dept. of Internal Medicine (내과학)
Journal Title
Antimicrobial Agents and Chemotherapy
Issued Date
2017
Volume
61
Issue
5
Keyword
doripenempopulation pharmacokineticsMonte Carlo simulationclearanceprobability of target attainmentprolonged infusionaugmented renal functionMIC
Abstract
We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20 to 50 ml/min or >50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (V/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CLCR. The proposed equation to estimate doripenem CL in Korean patients was CL/WT = 0.109 × WT × (CLCR/57)0.688, where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was ≤1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.
Keimyung Author(s)(Kor)
진규복
Publisher
School of Medicine
Citation
Dong-Hwan Lee et al. (2017). Population pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections. Antimicrobial Agents and Chemotherapy, 61(5), e02185–e02185. doi: 10.1128/AAC.02185-16.
Type
Article
ISSN
0066-4804
DOI
10.1128/AAC.02185-16.
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32356
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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