Challenges for drug studies in children: CYP3A phenotyping as example.
A paucity of data exists on the disposition and effect of drugs in young children. This information gap can be reduced by elucidating developmental principles of absorption, distribution, metabolism and excretion (ADME) in vivo. Such knowledge might enable the prediction of the disposition of individual drugs in children over the whole pediatric age range. CYP3A, the most abundant human drug metabolizing enzyme, is involved in the metabolism of more than 50% of all marketed drugs. Hence, elucidating the developmental pattern of CYP3A in relation to genetic background, disease and comedications might greatly enhance our knowledge on drug disposition in children. Several methods have been used to determine in vivo CYP3A activity in human adults, while similar studies in children face several ethical, practical and scientific challenges. The aim of this review is to identify these challenges and offer feasible solutions for studying drugs in young children, with an emphasis on CYP3A phenotyping as an example.
de Wildt
Saskia N
SN
Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. s.dewildt@utoronto.ca
Ito
Shinya
S
Koren
Gideon
G
D000328:Adult; D000367:Age Factors; D002648:Child; D002986:Clinical Trials as Topic / Q000941:ethics / Q000379:methods*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D010641:Phenotype
D004364:Pharmaceutical Preparations; D051544:Cytochrome P-450 CYP3A