The Role of Drug Metabolizing Enzymes in the Pathogenesis Adverse Drug Reactions in Children
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Seizures
- Sponsor
- Children's Mercy Hospital Kansas City
- Enrollment
- 274
- Locations
- 3
- Primary Endpoint
- Drug (Valproic Acid or Carbamazepine) Metabolite Profiles in Urine
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of the study is to examine the individual metabolic profiles of pediatric patients receiving carbamazepine or valproate therapy, in an attempt to determine identities of the reactive metabolites or, alternatively, the identities of those metabolites that serve as potential precursors to reactive species.
Detailed Description
Adverse drug reactions can be broadly defined as any undesirable response associated with therapeutic drug use. A simple and clinically useful classification is to divide adverse events into those that are dose-dependent and largely predictable from the known pharmacologic properties of the compound in question, and those that are dependent on characteristics unique to susceptible individuals, or idiosyncratic in nature. The long term objective of this research is to characterize the mechanisms responsible for the pathogenesis of idiosyncratic hypersensitivity reactions in children, particularly those involving carbamazepine and other aromatic anticonvulsants. The study is divided into two phases. Phase 1 of the study involves collecting urine from 50 patients taking CBZ therapeutically. Participants will be asked to provide a spot urine sample during routine health visits. The urine will be analyzed for the presence of CBZ and its metabolites. In Phase 2 of the study, urine will be collected from patients taking either CBZ or VPA therapeutically. If blood samples are drawn from these patients for medical purposes not related to this study the residual blood sample will be recovered before it is discarded for use in genotyping analysis. Participants will be asked to provide a urine sample covering one complete dosing interval of CBZ or VPA (preferably overnight). Patients will also be followed longitudinally, with urine collections at each clinic visit over at least a two year period.
Investigators
Steve Leeder
Pharm.D; Ph.D
Children's Mercy Hospital Kansas City
Eligibility Criteria
Inclusion Criteria
- •Pediatric patients of both genders between 1 and 16 years of age receiving CBZ or VPA mono-therapy will be recruited for this study. Additionally, for those patients who are receiving drugs other than CBZ or VPA to control their seizures, if CBZ or VPA are subsequently added to their treatment regimen, then these patients will also be recruited for this study.
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Drug (Valproic Acid or Carbamazepine) Metabolite Profiles in Urine
Time Frame: urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years
1. To examine the individual metabolic profiles of pediatric patients receiving carbamazepine or valproate therapy, in an attempt to determine the identities of the reactive metabolites or, alternatively, the identities of those metabolites that serve as potential precursors to reactive species (e.g., through conjugation with detoxifying compounds such as glutathione).
Secondary Outcomes
- Age-related Changes in Bioactivation(urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years)