作者
Catherijne AJ Knibbe, Elke HJ Krekels, Johannes N van den Anker, Joost DeJongh, Gijs WE Santen, Monique van Dijk, Sinno HP Simons, Richard A van Lingen, Evelyne M Jacqz-Aigrain, Meindert Danhof, Dick Tibboel
发表日期
2009/6
期刊
Clinical pharmacokinetics
卷号
48
页码范围
371-385
出版商
Springer International Publishing
简介
Background and objective
A considerable amount of drug use in children is still unlicensed or off-label. In order to derive rational dosing schemes, the influence of aging on glucuronidation capacity in newborns, including preterms, infants and children under the age of 3 years was studied using morphine and its major metabolites as a model drug.
Methods
A population pharmacokinetic model was developed with the nonlinear mixed-effects modelling software NONMEM® V, on the basis of 2159 concentrations of morphine and its glucuronides from 248 infants receiving intravenous morphine ranging in bodyweight from 500 g to 18 kg (median 2.8 kg). The model was internally validated using normalized prediction distribution errors.
Results
Formation clearances of morphine to its glucuronides and elimination …
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