Simulations of Valproate Doses Based on an External Evaluation of Pediatric Population Pharmacokinetic Models

2018 ◽  
Vol 59 (3) ◽  
pp. 406-417 ◽  
Author(s):  
Manon Tauzin ◽  
Jean-Marc Tréluyer ◽  
Rima Nabbout ◽  
Thierry Billette de Villemeur ◽  
Isabelle Desguerre ◽  
...  
Keyword(s):  
Pediatric Population ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation

scholarly journals External Evaluation of Population Pharmacokinetic Models and Bayes-Based Dosing of Infliximab

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1191
Author(s):  
Celine Konecki ◽  
Catherine Feliu ◽  
Yoann Cazaubon ◽  
Delphine Giusti ◽  
Marcelle Tonye-Libyh ◽  
...  
Keyword(s):  
Goodness Of Fit ◽  
Inflammatory Diseases ◽  
Plasma Concentrations ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation ◽  
Immunomodulatory Treatment ◽  
Weighted Residuals ◽  
Prediction Distribution ◽  
Target Plasma

Despite the well-demonstrated efficacy of infliximab in inflammatory diseases, treatment failure remains frequent. Dose adjustment using Bayesian methods has shown in silico its interest in achieving target plasma concentrations. However, most of the published models have not been fully validated in accordance with the recommendations. This study aimed to submit these models to an external evaluation and verify their predictive capabilities. Eight models were selected for external evaluation, carried out on an independent database (409 concentrations from 157 patients). Each model was evaluated based on the following parameters: goodness-of-fit (comparison of predictions to observations), residual error model (population weighted residuals (PWRES), individual weighted residuals (IWRES), and normalized prediction distribution errors (NPDE)), and predictive performances (prediction-corrected visual predictive checks (pcVPC) and Bayesian simulations). The performances observed during this external evaluation varied greatly from one model to another. The eight evaluated models showed a significant bias in population predictions (from −7.19 to 7.38 mg/L). Individual predictions showed acceptable bias and precision for six of the eight models (mean error of −0.74 to −0.29 mg/L and mean percent error of −16.6 to −0.4%). Analysis of NPDE and pcVPC confirmed these results and revealed a problem with the inclusion of several covariates (weight, concomitant immunomodulatory treatment, presence of anti-drug antibodies). This external evaluation showed satisfactory results for some models, notably models A and B, and highlighted several prospects for improving the pharmacokinetic models of infliximab for clinical-biological application.

External evaluation of published population pharmacokinetic models of polymyxin B

2021 ◽  
Author(s):  
Ya-qian Li ◽  
Kai-feng Chen ◽  
Jun-jie Ding ◽  
Hong-yi Tan ◽  
Nan Yang ◽  
...  
Keyword(s):  
Polymyxin B ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation

scholarly journals External evaluation of population pharmacokinetic models for ciclosporin in adult renal transplant recipients

2017 ◽  
Vol 84 (1) ◽  
pp. 153-171 ◽  
Author(s):  
Jun-Jun Mao ◽  
Zheng Jiao ◽  
Hwi-Yeol Yun ◽  
Chen-Yan Zhao ◽  
Han-Chao Chen ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Population Pharmacokinetic ◽  
Renal Transplant Recipients ◽  
Pharmacokinetic Models ◽  
Transplant Recipients ◽  
External Evaluation

scholarly journals Towards Rational Dosing Algorithms for Vancomycin in Neonates and Infants Based on Population Pharmacokinetic Modeling

2015 ◽  
Vol 60 (2) ◽  
pp. 1013-1021 ◽  
Author(s):  
Esther J. H. Janssen ◽  
Pyry A. J. Välitalo ◽  
Karel Allegaert ◽  
Roosmarijn F. W. de Cock ◽  
Sinno H. P. Simons ◽  
...  
Keyword(s):  
Pediatric Population ◽  
External Validation ◽  
Population Pharmacokinetic ◽  
Target Area ◽  
Pharmacokinetic Models ◽  
Time Curve ◽  
Population Pharmacokinetic Modeling ◽  
Model Based ◽  
Dosing Algorithm ◽  
Dosing Regimens

ABSTRACTBecause of the recent awareness that vancomycin doses should aim to meet a target area under the concentration-time curve (AUC) instead of trough concentrations, more aggressive dosing regimens are warranted also in the pediatric population. In this study, both neonatal and pediatric pharmacokinetic models for vancomycin were externally evaluated and subsequently used to derive model-based dosing algorithms for neonates, infants, and children. For the external validation, predictions from previously published pharmacokinetic models were compared to new data. Simulations were performed in order to evaluate current dosing regimens and to propose a model-based dosing algorithm. The AUC/MIC over 24 h (AUC24/MIC) was evaluated for all investigated dosing schedules (target of >400), without any concentration exceeding 40 mg/liter. Both the neonatal and pediatric models of vancomycin performed well in the external data sets, resulting in concentrations that were predicted correctly and without bias. For neonates, a dosing algorithm based on body weight at birth and postnatal age is proposed, with daily doses divided over three to four doses. For infants aged <1 year, doses between 32 and 60 mg/kg/day over four doses are proposed, while above 1 year of age, 60 mg/kg/day seems appropriate. As the time to reach steady-state concentrations varies from 155 h in preterm infants to 36 h in children aged >1 year, an initial loading dose is proposed. Based on the externally validated neonatal and pediatric vancomycin models, novel dosing algorithms are proposed for neonates and children aged <1 year. For children aged 1 year and older, the currently advised maintenance dose of 60 mg/kg/day seems appropriate.

External evaluation of population pharmacokinetic models for continuous administration of meropenem in critically ill adult patients

2020 ◽  
Vol 76 (9) ◽  
pp. 1281-1289
Author(s):  
YL. Wang ◽  
R. Guilhaumou ◽  
O. Blin ◽  
L. Velly ◽  
Amélie Marsot
Keyword(s):  
Critically Ill ◽  
Adult Patients ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation ◽  
Continuous Administration

scholarly journals External Evaluation of Population Pharmacokinetic Models of Imatinib in Adults Diagnosed with Chronic Myeloid Leukaemia

2021 ◽  
Author(s):  
Álvaro Corral Alaejos ◽  
Aránzazu Zarzuelo Castañeda ◽  
Silvia Jiménez Cabrera ◽  
Fermín Sánchez‐Guijo ◽  
María José Otero ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation

External evaluation of the predictive performance of seven population pharmacokinetic models for phenobarbital in neonates

2021 ◽  
Author(s):  
Sunae Ryu ◽  
Woo Jin Jung ◽  
Zheng Jiao ◽  
Jung‐Woo Chae ◽  
Hwi‐yeol Yun
Keyword(s):  
Predictive Performance ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Models ◽  
External Evaluation

scholarly journals External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings

2013 ◽  
Vol 75 (4) ◽  
pp. 1068-1080 ◽  
Author(s):  
Wei Zhao ◽  
Florentia Kaguelidou ◽  
Valérie Biran ◽  
Daolun Zhang ◽  
Karel Allegaert ◽  
...  
Keyword(s):  
Population Pharmacokinetic ◽  
Clinical Settings ◽  
Pharmacokinetic Models ◽  
External Evaluation
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