Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body

NCT ID: NCT00117715

Last Updated: 2017-09-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 121 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2000-10-31
• Study Completion Date: 2010-01-31

Brief Summary

This is a drug metabolism study in one-year old children involving caffeine and dextromethorphan.

Detailed Description

For many years, it has been considered dogma that drug biotransformation capability is limited at best in the fetus and newborn but increases over the first year of life to levels in toddlers and young children that generally exceed adult capacity. There are several situations where examination of clinical PK data has revealed discernable patterns of drug clearance that can be attributed to developmental differences in drug biotransformation. It has become apparent that there are developmental differences in expression among drug metabolizing enzyme families (cytochromes P450 or "CYPs", etc.) Furthermore, individual drug metabolizing enzymes with in a family may have unique developmental profiles that influence the therapeutic response, desired or undesired, to a given agent.

All subjects will have a single 5 ml venous blood sample taken upon admission to the study. All subjects will be given a single oral dose of caffeine and dextromethorphan. Patients will be allowed to consume their normal age appropriate diet around the time of study drug administration and through the sample collection periods. All spontaneously voided urine will be collected for a period of 12 hours following the caffeine and dextromethorphan administration

The specific aim of this proposal is to extend the current longitudinal investigation into the preschool age group (1 to 5 years of age). The developmental profile of CYPs, 1A2, 2D6, and 3A4 will be determined by caffeine and dextromethorphan phenotyping procedures. The purpose of this study is to determine the age/developmental stage at which the CYP2 1A2, 2D6 and 3A4 activities exceed adult activities.

Conditions

Healthy

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

Genotyping and Phenotyping using dextromethorphan and caffeine as probes

Single doses of dextromethorphan (0.3 mg/kg)and caffeine (3.0 mg/kg) are administered and urine is collected overnight for measurement of drug and metabolites to determine drug biotransformation activity.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Healthy children 12 months of age at enrollment

Exclusion Criteria

• Height and weight ratio outside of the 5th to 100th percentile for adjusted age
• Historical and/or biochemical evidence of hepatic, renal, or hematopoetic dysfunction
• Historical or physical evidence of a neurologic disease/condition (excluding simple, febrile seizures)
• Historical or physical evidence of any disorder associated with swallowing and/or gastrointestinal function
• Concomitant therapy with drugs or other products known to alter the activity of hepatic or intestinal microsomal enzymes(e.g., inducers or inhibitors of CYPs 1A2, 2D6, and/or 3A4), P-glycoprotein or potential competing substrates for the CYPs, under study within 7 days of a scheduled phenotyping evaluation
• Evidence of behavioral, developmental, or psychosocial conditions in the subjects and/or parents/caregivers that, in the opinion of the investigator, would have the potential to adversely impact the level of compliance required for successful study completion
• Evidence of geographic instability (i.e., moving of primary residence within last 24 months) that would adversely influence compliance with repeated study visits necessary for completion of the protocol
• Lack of telephone access required to insure adequate subject contact/follow-up
• Inability to obtain written informed consent from the subject's parents/guardians

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: collaborator

Children's Mercy Hospital Kansas City

OTHER

Sponsor Role: lead

Responsible Party

Steve Leeder

Pharm.D; Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J. Steven Leeder, Pharm. D, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Hospital Kansas City

Locations

Children's Mercy Hospital

Kansas City, Missouri, United States

Countries

United States

Other Identifiers

Internal IRB #P00 06-46

Identifier Type: -

Identifier Source: secondary_id

PPRU 10390

Identifier Type: -

Identifier Source: org_study_id