Pathogenesis of Adverse Drug Reactions

Condition(s) targeted: Seizures

Intervention: Urine Collection (Procedure)

Phase: N/A

Status: Recruiting

Sponsored by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Official(s) and/or principal investigator(s):
J. Steven Leeder, Pharm.D., Ph.D.,, Principal Investigator, Affiliation: Children's Mercy Hospital

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.

Official title: The Role of Drug Bioactivation and Detoxification in the Pathogenesis of Adverse Drug Reactions in Children

Study design: Screening, Longitudinal, Defined Population, Prospective Study

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.

Minimum age: 1 Year. Maximum age: 16 Years. Gender(s): Both.

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:

- None

Kosair Children's Hospital, Louisville, Kentucky 40202, United States; Recruiting
Elizabeth McDowell, RN, Phone: 502-629-5606
Mary Jane Kennedy, Pharm.D., Principal Investigator

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
J. Steven Leeder, Pharm.D, Ph.D., Phone: 816-234-3059
J.Steven Leeder, Pharm.D., Ph.D., Principal Investigator

Primary Children's Hospital, Pediatric Neurology, Salt Lake City, Utah 84113, United States; Recruiting
Rachel Brodis, Phone: 801-585-9072, Email: rachel.brodis@hsc.utah.edu
James F. Bale, M.D., Principal Investigator

Pediatric Pharmacology Research Units Website

Starting date: August 2002
Last updated: June 19, 2007