Developmental Regulation of Proteins Responsible for Transforming Drugs in the Body
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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 |
- 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) |
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Procedure: Genotyping and Phenotyping using dextromethorphan and caffeine as probes
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 |
Healthy children 12 months of age at study entry. Followed longitudinally until 5 uears of age.
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| United States, Missouri | |
| Children's Mercy Hospital | |
| Kansas City, Missouri, United States, 64108 | |
| 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 May 23, 2013