Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Steve Leeder, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier:
NCT00117715
First received: July 6, 2005
Last updated: April 29, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention
Healthy
Procedure: Genotyping and Phenotyping using dextromethorphan and caffeine as probes

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Developmental Regulation of CYPs 1A2, 2D6, 3A4

Resource links provided by NLM:


Further study details as provided by Children's Mercy Hospital Kansas City:

Primary Outcome Measures:
  • Change in drug metabolism phenotype with age [ Time Frame: 1-5 years ] [ Designated as safety issue: No ]
    Concentrations of specific drug metabolites in urine are used to estimate the activity of cytochromes P450 2D6, 3A4 and 1A2. The longitudinal study design allows for changes in drug metabolism activity with increasing age to be characterized.


Biospecimen Retention:   Samples With DNA

Urine DNA (source: blood or saliva)


Enrollment: 121
Study Start Date: October 2000
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
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.

  Eligibility

Ages Eligible for Study:   12 Months to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Healthy children 12 months of age at study entry. Followed longitudinally until 5 uears of age.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00117715

Locations
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
Investigators
Principal Investigator: J. Steven Leeder, Pharm. D, Ph.D. Children's Mercy Hospital-Kansas City, MO
  More Information

Additional Information:
No publications provided

Responsible Party: Steve Leeder, Pharm.D; Ph.D., Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT00117715     History of Changes
Other Study ID Numbers: PPRU 10390, Internal IRB #P00 06-46
Study First Received: July 6, 2005
Last Updated: April 29, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Mercy Hospital Kansas City:
Developmental regulation of CYPs 1A2, 2D6, 3A4
Ontogeny
pharmacokinetics
drug biotransformation
enzymatic biotransformation of drugs

Additional relevant MeSH terms:
Caffeine
Dextromethorphan
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 20, 2014