Biomarkers of CYP2D6 and CYP3A4 Variability in Pediatrics
Cytochrome P450 2D6 (CYP2D6) is an important enzyme in the body for breaking down many medications that are commonly used in children of various ages. The purpose of this proposal is to investigate the relative roles of development and genetic variation in CYP2D6 activity in school-aged children and adolescents with attention deficit and hyperactivity disorder and health controls using the over-the-counter cough suppressant, dextromethorphan or "DM", a standard probe for determining CYP2D6 phenotype. Embedded in the study design are sub-studies to search for by-products of normal body metabolism that reflect differences in enzyme activity, and a pharmacokinetic study to assess the consequences of CYP2D6 genetic variation on the systemic exposure to medications used by this patient population. Ultimately, the goal of the research is to personalize the use of medications in children by selecting the appropriate dose of the correct medication for individual patients.
Drug Metabolism Phenotype
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Exogenous and Endogenous Biomarkers of CYP2D6 and CYP3A4 Variability in Pediatrics|
- Characterize the change in CYP2D6 and CYP3A4 phenotype through adolescence [ Time Frame: Three years ] [ Designated as safety issue: No ]Growth and development adds an additional level of complexity as the genotype-phenotype relationship may change as children grow and develop. The purpose of this proposal is to characterize the relative roles of ontogeny and genetic variation towards changes in CYP2D6 and CYP3A4 activity during adolescence. Because some drugs commonly used to treat ADHD are metabolized by CYP2D6 and CYP3A4, the information gained from this study will contribute to a better understanding of the dosage requirements of medications used in this patient population.
- Identify endogenous markers of CYP2D6 activity [ Time Frame: Three years ] [ Designated as safety issue: No ]Metabolomic strategies (HPLC-MS/MS) will be utilized to identify and characterize endogenous compounds that correlate with the formation of dextrorphan (CYP2D6 activity)from the parent compound, dextromethorphan, administered as a phenotyping probe.
Biospecimen Retention: Samples With DNA
Blood or saliva for DNA testing. Blood samples will be obtained for safety labs throughout the study.
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||April 2016|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Pediatric patients who have a primary diagnosis of ADHD, combined type, hyperactive impulsive, or inattentive type (ADD).
Healthy subjects: Age and gender matched subjects who do not meet any of the exclusion criteria
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01118858
|United States, Missouri|
|The Children's Mercy Hospital|
|Kansas City, Missouri, United States, 64108|
|United States, Washington|
|The University of Washington|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Steven Leeder, PharmD, PhD||The Children's Mercy Hospital|