Maturation of cytochrome P450 3A mediated drug metabolism: Towards individualized dosing in children
Ontwikkeling van cytochroom P450 3A gemedieerd metabolisme van geneesmiddelen: De weg naar individueel doseren bij kinderen
Most drugs have not been adequately studied in children, leaving this population at an increased risk of underdosing or toxicity. Because of ethical, practical and financial constraints of pediatric clinical trials, there is a high percentage of drugs that is used in an unlicensed or off-label manner, with percentages approximating 70% in children and more than 93% in critically ill neonates. The main limitations in designing and conducting clinical studies in children are ethical, practical and scientific. Ethical issues are e.g. proxy consent, safety concerns and blood volume needed for pharmacokinetics. Practical issues pertain to the limited number of patients available and sample collection challenges. Scientific issues are related to the impact of growth and development on drug disposition, while increasingly attention is put on the long-term impact of early-life drug exposure on the developing brain. In the past the emphasis has been on the evaluation of the short-term direct effects of drugs, such as the increase in blood pressure upon the administration of vasoactive drugs. Fortunately, the current interest in primary outcome measures of drug treatment has led to an increase in the number of studies investigating long-term effects, i.e. neurodevelopmental outcome in children. An example is the recent study in which long-term cardiovascular effects of dobutamine and dopamine have been compared in preterm and low birth weight neonates.
|Keywords||maturation, metabolism, children|
|Promotor||D. Tibboel (Dick) , C.A.J. Knibbe (Catherijne)|
|Publisher||Erasmus University Rotterdam|
|Sponsor||Printing of this thesis has been financially supported by: Simcyp® (a Certara® company) Janssen Research & Development (a Johnson & Johnson company)|
Ince, I. (2013, November 29). Maturation of cytochrome P450 3A mediated drug metabolism: Towards individualized dosing in children. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/50146