Different Vancomycin Immunoassays Contribute to the Variability in Vancomycin Trough Measurements in Neonates

Samardžić, Janko; Smits, Anne; Spriet, Isabel; Soldatović, Ivan; Atkinson, Andrew; Bajcetic, Milica; Anker, John N. van den; Allegaert, Karel

doi:10.1155/2016/1974972

Cited by 11 publications

(5 citation statements)

References 13 publications

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“…In addition, we found no differences in PK parameters with respect to the different vancomycin assay methods used (i.e. assays based on fluorescence polarisation or turbidimetric inhibition principles) [45]. Supportive evidence for these findings is provided in Figs.…”

Section: Discussionsupporting

confidence: 76%

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations

et al. 2019

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Background and Objectives Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups. Methods A pooled population-pharmacokinetic model was built in NONMEM based on data from 14 different studies in different patient populations. Steady-state exposure was simulated and compared across patient subgroups for two US Food and Drug Administration/European Medicines Agency-approved drug labels and optimised doses were derived. Results The final model uses postmenstrual age, weight and serum creatinine as covariates. A 35-year-old, 70-kg patient with a serum creatinine level of 0.83 mg dL −1 (73.4 µmol L −1) has a V 1 , V 2 , CL and Q 2 of 42.9 L, 41.7 L, 4.10 L h −1 and 3.22 L h −1. Clearance matures with age, reaching 50% of the maximal value (5.31 L h −1 70 kg −1) at 46.4 weeks postmenstrual age then declines with age to 50% at 61.6 years. Current dosing guidelines failed to achieve satisfactory steady-state exposure across patient subgroups. After optimisation, increased doses for the Food and Drug Administration label achieve consistent target attainment with minimal (± 20%) risk of under-and over-dosing across patient subgroups. Conclusions A population model was developed that is useful for further development of age and kidney function-stratified dosing regimens of vancomycin and for individualisation of treatment through therapeutic drug monitoring and Bayesian forecasting.

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Section: Discussionsupporting

confidence: 76%

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations

et al. 2019

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“…We refer to the original studies for additional factual information. [14][15][16][17][18][19][20][21][22][23][24][25][26] Population PK analysis…”

Section: Study Populationmentioning

confidence: 99%

Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants

Jacqz-Aigrain

Leroux

Thomson

et al. 2019

Journal of Antimicrobial Chemotherapy

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Objectives In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mg·h/L at steady-state in at least 80% of neonates. Results A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <35 weeks PMA and 15 mg/kg q8h if ≥35 weeks PMA) achieved the AUC0–24 target earlier than a standard ‘Blue Book’ dosage regimen in >89% of the treated patients. Conclusions The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc.

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“…on the relevance of a given assay have also been reported in neonates.Using the same vancomycin dosing regimens and confirming similarity in clinical characteristics, vancomycin trough concentrations measured by PETINIA (2011-2012, n=400) were 20% lower, with a mean difference of 1.93 mg/l compared to COBAS (2012-2014, n=352)[78]. Furthermore, Zhao et al quantified the predictive performance of 6 published vancomycin PK models when applied to a new dataset, and observed that performance in part related to the vancomycin assay[48].…”

mentioning

confidence: 70%

Pharmacokinetic modelling and Bayesian estimation-assisted decision tools to optimize vancomycin dosage in neonates: only one piece of the puzzle

Allegaert

Flint

Smits

2019

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Vancomycin is commonly administered to neonates, while observational data on therapeutic drug monitoring (TDM, trough levels) suggest that vancomycin exposure and dosage remain substandard.Area covered: Data on vancomycin pharmacokinetics (PK) and its covariates are abundant. Consequently, modelling is an obvious tool to improve targeted exposure, with a shift from TDM trough levels to area under the curve (AUC 24h ) targets, as in adults. Continuous administration appeared as practice to facilitate AUC 24h target attainment, while Bayesian model-supported targeting emerged as novel tool.However, the AUC 24h /MIC (minimal inhibitory concentration) target itself should consider neonate specific aspects (bloodstream infections, coagulase-negative staphylococci, protein binding, underexplored causes of variability, like assays, preparation and administration inaccuracies, or missing covariates). Expert opinion:To improve targeted exposure in neonates, initial vancomycin prescription should be based on 'a priori model based individual dosing' using validated dosing regimens, followed by further tailoring by dosing optimization applying Bayesian estimation-assisted TDM. Future research should focus on feasibility to integrate these tools (individualized dosing, Bayesian models) in clinical practice, and to perform PK/PD studies in the relevant animal models and human neonatal setting (coagulase-negative staphylococci, blood stream infections).

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Different Vancomycin Immunoassays Contribute to the Variability in Vancomycin Trough Measurements in Neonates

Cited by 11 publications

References 13 publications

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations

Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants

Pharmacokinetic modelling and Bayesian estimation-assisted decision tools to optimize vancomycin dosage in neonates: only one piece of the puzzle

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