Pediatric Dose Selection and Utility of PBPK in Determining Dose.
AAPS J
; 20(2): 31, 2018 02 13.
Article
en En
| MEDLINE
| ID: mdl-29441439
ABSTRACT
Interest in determining safe and efficacious doses for drug administration in pediatric patients has increased dramatically in recent years. However, published pediatric clinical studies have failed to increase proportionally with adult clinical study publications. In order to assess the current state of pediatric dose determination and the supporting role of physiologically based pharmacokinetic modeling and simulation in determining pediatric dose, the pediatric clinical literature (2006-2016) and case examples of pediatric PBPK modeling efforts were reviewed. The objective of this assessment was to investigate the contribution of PBPK to our understanding of the differences between children and adults, which lead to differences in drug dose. Pediatric and adult dose data were available for 31 small molecule drugs. In general, pediatric dose was well-correlated with adult data, with an apparent tendency for higher body weight- or body surface area-normalized pediatric dose. Overall performance of pediatric PBPK modeling approaches was considered to adequately predict observed data. However, model performance was dependent upon age group simulated, with approximately half of neonatal predictions falling outside of 1.5-fold of observed. In conclusion, there is a clear need for further refinement of starting dose in pediatric phase 1 studies, and utilization of PBPK could lead to reduced numbers of patients required to establish safe and efficacious doses in the pediatric population.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farmacocinética
/
Preparaciones Farmacéuticas
/
Modelos Biológicos
Tipo de estudio:
Evaluation_studies
/
Prognostic_studies
Límite:
Adult
/
Child
/
Humans
Idioma:
En
Revista:
AAPS J
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA