An Update on Population Pharmacokinetic Analyses of Vancomycin, Part I: In Adults

Aljutayli, Abdullah; Marsot, Amélie; Nekka, Fahima

doi:10.1007/s40262-020-00866-2

Cited by 62 publications

(76 citation statements)

References 55 publications

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“…It can be used to quantitatively investigate the effects of related factors such as sex, age, gene variation, liver and kidney function, combined diseases, combined drugs and random effects on pharmacokinetics [11,12] . It can obtain pharmacokinetic models and parameters while understanding the pharmacokinetic characteristics of drugs.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of metoprolol in Chinese post-PCI patients

Chen¹,

Hong²,

Zhao³

et al. 2020

Preprint

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Aims: Metoprolol (MET) is widely used in post-PCI patient. This study aimed to establishment a new population pharmacokinetic (PPK) model of MET in Chinese post-PCI patients. Methods: Blood samples from subjects were collected and the CYP2D6*10 genotyping was detected by gene chip. The plasma concentration of MET was determined by LC-MS/MS. The PPK model of MET was developed by using NONMEM method. Pharmacogenetic analysis was carried out in the CYP2D6*10 genotyping. Results: Based on the data of 43 patients with coronary heart disease (CHD) after PCI, the final PPK model of MET was established as follows: ; . A covariate analysis showed that only the CYP2D6 gene mutation had a significantly effect on the MET clearance rate. The CYP2D6*10 mutation could reduce the MET clearance rate. Compared with the CYP2D6*1*1 genotype the CYP2D6*1*10 genotype decreased by 36.6%, the CYP2D*10/*10 decreased by 70.7% and showing a gene dose effect. Conclusions: The PPK model of MET established in this study is stable and reliable, which can provide reference for individual administration of MET. In Chinese patients with CHD after PCI, CYP2D6*10 gene mutation is one of the important factors affecting the MET clearance rate. 1.Background:Metoprolol (MET) is the most commonly used selective β1 receptor antagonist in the treatment of CHD. Almost all of MET is metabolized in the liver, and CYP2D6 mediates 70%-80% of MET metabolism [1] . In Chinese clinical practice, the dose of β-blockers in patients after PCI is seriously insufficient. In the results of China PEACE study, the daily dose of metoprolol tartrate tablets in AMI patients was [?]25mg [2] . This may be due to a variety of reasons, such as excessive consideration of the side effects of β-blockers, short hospitalization days, etc., but it may be related to the high CYP2D6*10 mutation rate in Chinese. CYP2D6 gene has significant genetic heterogeneity, of which nearly 100 mutants have been found so far [3] . Gene variation can affect the number and activity of coding enzymes. Several studies have confirmed that changes in pharmacokinetic parameters of MET are associated with CYP2D6 gene polymorphism [4][5][6] . However, there are obvious regional differences in CYP2D6 gene variation.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of metoprolol in Chinese post-PCI patients

Chen¹,

Hong²,

Zhao³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…The PopPK model can estimate the pharmacokinetic parameters by combining the intra-individual and inter-individual variability that is important for optimizing the dosage schedule of vancomycin. 6 The PopPK model is based on therapeutic drug monitoring (TDM). TDM focuses on the drug concentration in patient's blood or other fluids, and develop an optimal dosing regimen based on pharmacokinetics parameters to improve efficacy and reduce adverse reactions.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

“…Vancomycin has a narrow therapeutic index and shows high inter‐individual variability, making the dosage adjustment challenging. The PopPK model can estimate the pharmacokinetic parameters by combining the intra‐individual and inter‐individual variability that is important for optimizing the dosage schedule of vancomycin 6 …”

Section: What Is Known and Objectivementioning

confidence: 99%

Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents

et al. 2021

J Clin Pharm Ther

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What is known and objectives: Various population pharmacokinetic (PopPK) models for vancomycin in children and adolescents have been constructed to optimize the therapeutic regimen of vancomycin. However, little is known about their predictive performance when extrapolated to different clinical centres. Therefore, the aim of this study was to externally validate the predictability of vancomycin PopPK model when extrapolated to different clinical centres and verify its applicability in an independent data set. Methods:The published models were screened from the literature and evaluated using an external data set of a total of 451 blood concentrations of vancomycin measured in 220 Chinese paediatric patients. Prediction-and simulation-based diagnostics and Bayesian forecasting were performed to evaluate the predictive performance of the models.Results: Ten published PopPK models were assessed. Prediction-based diagnostics showed that none of the investigated models met all the standards (median prediction error (MDPE) ≤ ±20%, median absolute prediction error (MAPE) ≤30%, PE% within ±20% (F 20 ) ≥35% and PE% within ±30% (F 30 ) ≥50%), indicating unsatisfactory predictability. In simulation-based diagnostics, both the visual predictive checks (VPC) and the normalized prediction distribution error (NPDE) indicated misspecification in all models. Bayesian forecasting results showed that the accuracy and precision of individual predictions could be significantly improved with one or two prior observations, but frequent monitoring might not be necessary in the clinic, since Bayesian forecasting identified that greater number of samples did not significantly improve the predictability. Model 3 established by Moffett et al showed better predictability than other models. What is new and conclusion:The 10 published models performed unsatisfactorily in prediction-and simulation-based diagnostics; none of the published models was | 821 LV et aL. How to cite this article: Lv C, Lu J, Jing L, et al. Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents. J

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“…We built one-compartment VCM models since they are non-inferior to two-and three-compartment models [29,34]:…”

Section: Populiation Pk Model Developmentmentioning

confidence: 99%

The Glomerular Filtration Rate Estimators in the Pharmacokinetic Modelling in Acute Kidney Injury: An Observational Study

et al. 2021

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The glomerular filtration rate (GFR), according to which the drug dose for patients with chronic kidney disease (CKD) is adjusted, is computed with estimators (eGFR) that are developed specifically for CKD. These particular types of estimators are also used in population pharmacokinetic (pop PK) modelling in drug development. Similar approaches without scientific validation have been proposed for patients with acute kidney injury (AKI), yet it is uncertain which specific eGFR should be used for drug dosing or in pop PK models in patients with AKI. In our study, we included 34 patients with AKI and vancomycin (VCM) treatment, and we built both individual PK and pop PK (non-linear mixed-effects, one-compartment) models to see which eGFR estimator is the best covariate. In these models different eGFRs (Cockcroft-Gault, MDRD, CKD-EPI 2009, Jelliffe and Jelliffe, Chen et al., and Yashiro et al. 2013) were used. We included six additional patients to validate the final pop PK model. All eGFRs underrate the true renal clearance in the AKI, so we created pop PK models for VCM dosing in AKI with all eGFRs, to discover that the most accurate model was the one with the Cockcroft-Gault estimator. Since the eGFRs underestimate the true renal clearance in AKI, they are inaccurate for clinical drug dosing decisions, with the exception of the Cockcroft-Gault one, which is appropriate for the pop PK models intended for drug development purposes in AKI.

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An Update on Population Pharmacokinetic Analyses of Vancomycin, Part I: In Adults

Cited by 62 publications

References 55 publications

Population pharmacokinetics of metoprolol in Chinese post-PCI patients

Population pharmacokinetics of metoprolol in Chinese post-PCI patients

Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents

The Glomerular Filtration Rate Estimators in the Pharmacokinetic Modelling in Acute Kidney Injury: An Observational Study

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