Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model

Department of Drug Design and Pharmacology

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model. / Knøsgaard, Katrine Rørbæk; Foster, David John Richard; Kreilgaard, Mads; Sverrisdóttir, Eva; Upton, Richard Neil; van den Anker, Johannes N.

In: European Journal of Pharmaceutical Sciences, 30.06.2016.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Knøsgaard, KR, Foster, DJR, Kreilgaard, M, Sverrisdóttir, E, Upton, RN & van den Anker, JN 2016, 'Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model', European Journal of Pharmaceutical Sciences. https://doi.org/10.1016/j.ejps.2016.06.026

APA

Knøsgaard, K. R., Foster, D. J. R., Kreilgaard, M., Sverrisdóttir, E., Upton, R. N., & van den Anker, J. N. (2016). Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model. European Journal of Pharmaceutical Sciences. https://doi.org/10.1016/j.ejps.2016.06.026

Vancouver

Knøsgaard KR, Foster DJR, Kreilgaard M, Sverrisdóttir E, Upton RN, van den Anker JN. Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model. European Journal of Pharmaceutical Sciences. 2016 Jun 30. https://doi.org/10.1016/j.ejps.2016.06.026

Author

Knøsgaard, Katrine Rørbæk ; Foster, David John Richard ; Kreilgaard, Mads ; Sverrisdóttir, Eva ; Upton, Richard Neil ; van den Anker, Johannes N. / Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model. In: European Journal of Pharmaceutical Sciences. 2016.

Bibtex

@article{73a68de092dc4756b0f442b639d5f188,

title = "Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model",

abstract = "Morphine is commonly used for pain management in preterm neonates. The aims of this study were to compare published models of neonatal pharmacokinetics of morphine and its metabolites with a new dataset, and to combine the characteristics of the best predictive models to design a meta-model for morphine and its metabolites in preterm neonates. Moreover, the concentration-analgesia relationship for morphine in this clinical setting was also investigated. A population of 30 preterm neonates (gestational age: 23-32weeks) received a loading dose of morphine (50-100μg/kg), followed by a continuous infusion (5-10μg/kg/h) until analgesia was no longer required. Pain was assessed using the Premature Infant Pain Profile. Five published population models were compared using numerical and graphical tests of goodness-of-fit and predictive performance. Population modelling was conducted using NONMEM{\textregistered} and the $PRIOR subroutine to describe the time-course of plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide, and the concentration-analgesia relationship for morphine. No published model adequately described morphine concentrations in this new dataset. Previously published population pharmacokinetic models of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were combined into a meta-model. The meta-model provided an adequate description of the time-course of morphine and the concentrations of its metabolites in preterm neonates. Allometric weight scaling was applied to all clearance and volume terms. Maturation of morphine clearance was described as a function of postmenstrual age, while maturation of metabolite elimination was described as a function of postnatal age. A clear relationship between morphine concentrations and pain score was not established.",

author = "Kn{\o}sgaard, {Katrine R{\o}rb{\ae}k} and Foster, {David John Richard} and Mads Kreilgaard and Eva Sverrisd{\'o}ttir and Upton, {Richard Neil} and {van den Anker}, {Johannes N}",

note = "Copyright {\textcopyright} 2016. Published by Elsevier B.V.",

year = "2016",

month = jun,

day = "30",

doi = "10.1016/j.ejps.2016.06.026",

language = "English",

journal = "Norvegica Pharmaceutica Acta",

issn = "0928-0987",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Pharmacokinetic models of morphine and its metabolites in neonates systematic comparisons of models from the literature, and development of a new meta-model

AU - Knøsgaard, Katrine Rørbæk

AU - Foster, David John Richard

AU - Kreilgaard, Mads

AU - Sverrisdóttir, Eva

AU - Upton, Richard Neil

AU - van den Anker, Johannes N

PY - 2016/6/30

Y1 - 2016/6/30

N2 - Morphine is commonly used for pain management in preterm neonates. The aims of this study were to compare published models of neonatal pharmacokinetics of morphine and its metabolites with a new dataset, and to combine the characteristics of the best predictive models to design a meta-model for morphine and its metabolites in preterm neonates. Moreover, the concentration-analgesia relationship for morphine in this clinical setting was also investigated. A population of 30 preterm neonates (gestational age: 23-32weeks) received a loading dose of morphine (50-100μg/kg), followed by a continuous infusion (5-10μg/kg/h) until analgesia was no longer required. Pain was assessed using the Premature Infant Pain Profile. Five published population models were compared using numerical and graphical tests of goodness-of-fit and predictive performance. Population modelling was conducted using NONMEM® and the $PRIOR subroutine to describe the time-course of plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide, and the concentration-analgesia relationship for morphine. No published model adequately described morphine concentrations in this new dataset. Previously published population pharmacokinetic models of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were combined into a meta-model. The meta-model provided an adequate description of the time-course of morphine and the concentrations of its metabolites in preterm neonates. Allometric weight scaling was applied to all clearance and volume terms. Maturation of morphine clearance was described as a function of postmenstrual age, while maturation of metabolite elimination was described as a function of postnatal age. A clear relationship between morphine concentrations and pain score was not established.

AB - Morphine is commonly used for pain management in preterm neonates. The aims of this study were to compare published models of neonatal pharmacokinetics of morphine and its metabolites with a new dataset, and to combine the characteristics of the best predictive models to design a meta-model for morphine and its metabolites in preterm neonates. Moreover, the concentration-analgesia relationship for morphine in this clinical setting was also investigated. A population of 30 preterm neonates (gestational age: 23-32weeks) received a loading dose of morphine (50-100μg/kg), followed by a continuous infusion (5-10μg/kg/h) until analgesia was no longer required. Pain was assessed using the Premature Infant Pain Profile. Five published population models were compared using numerical and graphical tests of goodness-of-fit and predictive performance. Population modelling was conducted using NONMEM® and the $PRIOR subroutine to describe the time-course of plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide, and the concentration-analgesia relationship for morphine. No published model adequately described morphine concentrations in this new dataset. Previously published population pharmacokinetic models of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were combined into a meta-model. The meta-model provided an adequate description of the time-course of morphine and the concentrations of its metabolites in preterm neonates. Allometric weight scaling was applied to all clearance and volume terms. Maturation of morphine clearance was described as a function of postmenstrual age, while maturation of metabolite elimination was described as a function of postnatal age. A clear relationship between morphine concentrations and pain score was not established.

U2 - 10.1016/j.ejps.2016.06.026

DO - 10.1016/j.ejps.2016.06.026

M3 - Journal article

C2 - 27373670

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

ER -

ID: 163755570