Physiologically Based Pharmacokinetic Modeling of Oxycodone in Children to Support Pediatric Dosing Optimization.
Pharm Res
; 36(12): 171, 2019 Oct 25.
Article
en En
| MEDLINE
| ID: mdl-31654287
ABSTRACT
PURPOSE:
Physiologically-based pharmacokinetic (PBPK) modeling offers a unique modality to predict age-specific pharmacokinetics. The objective of this study was to assess the ability of PBPK model to predict plasma exposure of oxycodone, a widely used opioid for pain management, in adults and children.METHODS:
A full PBPK model of oxycodone following intravenous and oral administration was developed using a 'bottom-up' and 'top-down' combined strategy. The model was then extrapolated to pediatrics through a reasonable scaling method. The adult and pediatric model was evaluated using data from 17 clinical PK studies by testing predicted/observed goodness of fit. The mean fold error for PK parameters was calculated. Finally, we used the validated PBPK model to visualize adult-children dose conversion for oxycodone.RESULTS:
The developed PBPK model successfully predicted the oxycodone disposition in adults, wherein the predicted versus observed AUC, Cmax, and tmax were within 0.90 to 1.20-fold difference. After scaling anatomy/physiology, protein binding, and clearance, the model showed satisfactory prediction performance for pediatric populations as predicted AUC were within the 1.50-fold range of the observed values. According to the application of PBPK model, we found that different intravenous doses should be given in children of different ages compared to a standard 0.1 mg/kg in adults, while a progressive increasing dose with age growth following oral administration is recommended for children.CONCLUSIONS:
The current example provides the opportunity for using the PBPK model to guide dose adjustment of oxycodone in the design of future pediatric clinical studies.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oxicodona
/
Analgésicos Opioides
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Humans
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Infant
/
Newborn
Idioma:
En
Año:
2019
Tipo del documento:
Article