ArticleClinical pharmacokinetics2011
Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children.
Article in Clinical pharmacokinetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Evidence-based morphine dosing for postoperative neonates and infants.Clinical pharmacokinetics · 2014Trial
- Codeine toxicity via breast Milk: Can this occur and implications for opiate therapy in children.British journal of clinical pharmacology · 2026Review
- The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling.Clinical pharmacokinetics · 2019Review
- Article
- Postoperative pain management in children and infants: an update.Paediatric drugs · 2014Review
- A novel maturation function for clearance of the cytochrome P450 3A substrate midazolam from preterm neonates to adults.Clinical pharmacokinetics · 2013Article
- Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model.Clinical drug investigation · 2013Article
- External Evaluation of Population Pharmacokinetic Models of Vancomycin in Neonates: The transferability of published models to different clinical settings.British journal of clinical pharmacology · 2013Article
- Prediction of morphine clearance in the paediatric population : how accurate are the available pharmacokinetic models?Clinical pharmacokinetics · 2012Review
- Fundamentals of population pharmacokinetic modelling: validation methods.Clinical pharmacokinetics · 2012Review
- Propofol Clearance in Morbidly Obese Children and Adolescents : Influence of Age and Body Size.Clinical pharmacokinetics · 2012Article
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Authors and funding
9 authors.
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Abstract
BACKGROUND AND
objectiveModel validation procedures are crucial when models are to be used to develop new dosing algorithms. In this study, the predictive performance of a previously published paediatric population pharmacokinetic model for morphine and its metabolites in children younger than 3 years (original model) is studied in new datasets that were not used to develop the original model.
methodsSix external datasets including neonates and infants up to 1 year were obtained from four different research centres. These datasets contained postoperative patients, ventilated patients and patients on extracorporeal membrane oxygenation (ECMO) treatment. Basic observed versus predicted plots, normalized prediction distribution error analysis, model refitting, bootstrap analysis, subpopulation analysis and a literature comparison of clearance predictions were performed with the new datasets to evaluate the predictive performance of the original morphine pharmacokinetic model.
resultsThe original model was found to be stable and the parameter estimates were found to be precise. The concentrations predicted by the original model were in good agreement with the observed concentrations in the four datasets from postoperative and ventilated patients, and the model-predicted clearances in these datasets were in agreement with literature values. In the datasets from patients on ECMO treatment with continuous venovenous haemofiltration (CVVH) the predictive performance of the model was good as well, whereas underprediction occurred, particularly for the metabolites, in patients on ECMO treatment without CVVH.
conclusionThe predictive value of the original morphine pharmacokinetic model is demonstrated in new datasets by the use of six different validation and evaluation tools. It is herewith justified to undertake a proof-of-principle approach in the development of rational dosing recommendations - namely, performing a prospective clinical trial in which the model-based dosing algorithm is clinically evaluated.
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