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Population-Based Pharmacokinetics and Dose Optimization of Imipenem in Vietnamese Critically-Ill Patients

Authors :
Dinh,Thanh D
Nguyen,Hung N
Le,Ba Hai
Nguyen,Thuy T T
Nguyen,Huong T L
Dinh,Thanh D
Nguyen,Hung N
Le,Ba Hai
Nguyen,Thuy T T
Nguyen,Huong T L
Publication Year :
2022

Abstract

Thanh D Dinh,1,2 Hung N Nguyen,1 Ba Hai Le,1 Thuy TT Nguyen,1 Huong TL Nguyen1 1Department of Clinical Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam; 2Phu Tho General Hospital, Việt Trì, Phu Tho Province, VietnamCorrespondence: Huong TL Nguyen, Department of Clinical Pharmacy, Hanoi University of Pharmacy, 13, 15 – Lê Thánh Tông, Hoà n Kiếm, Hà Nội, 100000, Vietnam, Tel +84904308406, Email huongntl@hup.edu.vnPurpose: The purpose of this study was to characterize the population-based pharmacokinetic (POP-PK) profile of imipenem in Vietnamese adult patients and to assess the probability of target attainment (PTA) of the pharmacokinetic/pharmacodynamic (PK/PD) parameter to determine the optimal dose.Patients and Methods: A POP-PK model of imipenem was developed in patients with severe infection from a 1500-bed general hospital in Vietnam, using MONOLIX 2019. After the initial dose infusion, 6 blood samples per patient were collected to measure plasma imipenem levels. Eight covariates (eg, age, weight) were investigated to ascertain their influence on imipenem’s PK. Monte Carlo simulations were performed to determine the PTA for the time in which the total steady-state imipenem concentrations remained above the MIC (T>MIC) for 40% and 100% of the dosing interval.Results: The best fit to the PK data was a two-compartment model with inter-individual variability (IIV) in clearance (CL), central volume of distribution (Vc), intercompartmental clearance (Q), and peripheral volume of distribution (Vp). Only creatinine clearance was retained as a covariate on CL in the final model. The typical value of CL and Vc were estimated to be 4.79 L/h and 11.1 L, respectively. The between-subject variability in this population was noted to be high (> 38%, especially for IIV on Q at 110%). Prolonged or continuous infusion demonstrated efficacy (40% T>MIC) against bacteria with a MIC of 4mg/L. To achieve 100% T>MIC or bacteria with MIC> 4 mg/L, howeve

Details

Database :
OAIster
Notes :
text/html, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1342153750
Document Type :
Electronic Resource