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Regul Toxicol Pharmacol ; 39(3): 282-309, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15135209

RESUMO

Whether children incur different risks from xenobiotics than adults will depend on the exposure, biokinetics, and dynamics of compound. In this paper, current knowledge on developmental physiology and possible effects on biokinetics are evaluated and the role of biokinetics in risk assessment both for drugs and chemicals is discussed. It is concluded that most dramatic age-related physiological changes that may affect biokinetics occur in the first 6-12 months of age. The difference in internal exposure between children and adults can generally be predicted from already known developmental physiological differences. However, for risk assessment it will also be necessary to determine whether internal exposure is within the drug's therapeutic window or if it will exceed the NOAEL of a chemical. Furthermore, the effects of internal exposure of potentially harmful compounds on developing organ systems is of utmost importance. However, knowledge on this aspect is very limited. Risk assessment in children could be improved by: (1) application of pediatric PBPK-models in order to gain insight into internal exposure in children, (2) studies in juvenile animals for studying effects on developing systems, and (3) extrapolation of knowledge on the relationship between internal exposure and dynamics for drugs to other chemicals.


Assuntos
Desenvolvimento Infantil/fisiologia , Modelos Biológicos , Preparações Farmacêuticas , Farmacocinética , Medição de Risco , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Fenômenos Fisiológicos do Sistema Digestório , Substâncias Perigosas/farmacocinética , Humanos , Lactente , Recém-Nascido , Fígado/enzimologia , Fígado/metabolismo , Metabolismo , Nível de Efeito Adverso não Observado , Fenômenos Fisiológicos Respiratórios , Absorção Cutânea , Distribuição Tecidual
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