Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections.
Antimicrob Agents Chemother
; 61(5)2017 05.
Article
em En
| MEDLINE
| ID: mdl-28223378
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Bacterianas
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Carbapenêmicos
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Antibacterianos
Tipo de estudo:
Health_economic_evaluation
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article