Population Pharmacokinetics and Dose Optimization of Ceftazidime and Imipenem in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Nguyen, Thu-Minh; Ngo, Thu-Hue; Quan, Truong Anh; Vu, Dinh Hoa; Le, Dinh-Chi; Vu, Ngan-Binh; Can, Tuyet-Nga; Anh, Nguyen Hoang; Phan, Thu-Phuong; Bambeke, Françoise Van; Vidaillac, Céline; Ngo, Quy-Chau

doi:10.3390/pharmaceutics13040456

Cited by 2 publications

(2 citation statements)

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“…3,[7][8][9] Another model which was published for chronic obstructive pulmonary Vietnamese patients based on sparse data with only 2 samples per patient used a one-compartment structural model. 4 In contrast, the rich sampling program includes 06 samples optimized by PFIM software, which was chosen to conduct our study. As a result of this sampling technique, the POP-PK obtained will be more accurate in describing the population and make fewer biased predictions than some studies due to biased sample methods (e.g, trough-only sampling).…”

Section: Discussionmentioning

confidence: 99%

“…In Viet Nam, there has been only one published POP-PK study on imipenem using a limited sampling strategy and evaluated in patients with acute exacerbations of chronic obstructive pulmonary. 4 Thus, a POP-PK model based on a comprehensive sampling technique would give more information for Monte Carlo simulations to determine appropriate dosage regimens of imipenem in critically-ill Vietnamese patients.…”

Section: Introductionmentioning

confidence: 99%

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

Dinh¹,

Nguyen²,

Le³

et al. 2022

IDR

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Purpose 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, however, the number of doses must be increased while maintaining the same daily dose for the 3-hour prolonged infusion regimen. Conclusion A population pharmacokinetic model of imipenem was developed for Vietnamese adult patients with severe illness. By using Monte Carlo simulation, the appropriate dose has been suggested based on the bacterial MIC value and the targeted PK/PD goal.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Dinh¹,

Nguyen²,

Le³

et al. 2022

IDR

View full text Add to dashboard Cite

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Population pharmacokinetics and dose optimization of ceftazidime in critically ill children

Li,

Gao,

Wang

et al. 2024

Front. Pharmacol.

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ObjectiveThe aim of this study was to develop a population pharmacokinetic model for ceftazidime in critically ill children in the pediatric intensive care unit (PICU) and optimize an appropriate dosing regimen for this population.MethodsWe performed a prospective pharmacokinetic study on critically ill children aged 0.03–15 years. A population pharmacokinetic model was developed using the NLME program. Statistical and graphical methods were used to assess the stability and predictive performance of the model. Monte Carlo simulations were conducted to determine the optimal ceftazidime dosing regimen to achieve 70% fT > minimum inhibitory concentration (MIC).ResultsThis study included 88 critically ill children and 100 ceftazidime serum concentrations. The pharmacokinetic characteristics of ceftazidime were best described by a one-compartment linear elimination model. The weight and estimated glomerular filtration rate (eGFR) were determinant covariates for the clearance (CL) of ceftazidime. The recommended ceftazidime dosage regimens achieved a probability of target attainment (PTA) >90% for critically ill children at MIC values of 2, 4, and 8 mg/L. For bacterial infection at an MIC of 16 mg/L, it is difficult to achieve effective pharmacodynamic (PD) targets in vivo with the commonly used dose of ceftazidime.ConclusionThe population pharmacokinetic model of ceftazidime was established in critically ill children. Based on this model, we recommend evidence-based, individualized dosing regimens for subgroups with different weights and renal functions. The current daily dosage for children adequately meets the treatment requirements for MICs of 2, 4, and 8 mg/L, while for bacterial infection at an MIC of 16 mg/L, an elevated dosage regimen may be required.Clinical Trial Registrationhttps://www.medicalresearch.org.cn/login, Identifier MR-42-22-000220.

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Population Pharmacokinetics and Dose Optimization of Ceftazidime and Imipenem in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Cited by 2 publications

References 50 publications

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

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

Population pharmacokinetics and dose optimization of ceftazidime in critically ill children

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