NCT00117715

Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body

Developmental Regulation of CYPs 1A2, 2D6, 3A4

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 121 (actual)
• Sponsor: Children's Mercy Hospital Kansas City · Academic / Other
• Sex: All
• Age: 12 Months – 5 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
PROCEDURE	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.

Timeline

• Start date: 2000-10-01
• Primary completion: 2010-01-01
• Completion: 2010-01-01
• First posted: 2005-07-08
• Last updated: 2017-09-12
• Results posted: 2017-08-14

Locations

1 site across 1 country: United States