CYP2D6 Polymorphism
Conditions
Brief summary
Specific Aim: To investigate if isotretinoin (13-cis-retinoic acid) administration decreases CYP2D6 activity in adolescent patients.
Detailed description
In this aim, we will conduct a drug-drug interaction study evaluating the effects of 13-cis-retinoic acid on non-induced CYP2D6 activity in adolescent patients. Secondary analysis will evaluate the relationship between retinoid concentrations and CYP2D6 activity in these special populations
Interventions
DRUGIsotretinoin
Drug interaction study
DRUGdextromethorphan
Drug interaction study
Sponsors
National Institute of General Medical Sciences (NIGMS)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Prospective, pre-post drug interaction study evaluating an approved drug (Phase 4) with a Phase 1 study design.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Non-pregnant * ≥ 12 years * Patients with severe acne that are expected to receive isotretinoin for therapeutic reasons
Exclusion criteria
* Weight \< 80 lbs * Allergy or adverse reaction to dextromethorphan, vitamin A or isotretinoin * Pregnant or planning to become pregnant * Unable to follow isotretinoin risk evaluation and mitigation strategies (REMS) program (also known as iPLEDGE program) * Chronic or persistent cough accompanying asthma, smoking or chronic obstructive pulmonary disease, * Productive cough, * Fever, * Known kidney disease, * Known liver disease, * Diabetes * Obesity, body mass index ≥ 30 kg/m2 * Bipolar disease, * Attention deficit disorder, * Social phobia, * Concurrent or use within 14 days of drugs known to interact with dextromethorphan or cytochrome P450 2D6 (CYP2D6) or drugs known to increase the risk of adverse effects from dextromethorphan * Concurrent use of any other product containing dextromethorphan * Consuming foods, beverages or dietary supplements known to interact with dextromethorphan or CYP2D6 * Unable to give written informed consent/assent, * Inability to fast for 4 hours prior to study. * Wards of the State
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CYP2D6 Activity as Measured by the Molar Concentration Ratio of Dextromethorphan (DM)/Dextrophan (DX) | 1 week to 6 months | dextromethorphan (DM)/dextrophan (DX) molar concentration Metabolic Ratio. The metabolic ratio is unit-less as the molar concentrations cancel out. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Group Individuals expected to receive isotretinoin for therapeutic reasons | 33 |
| Total | 33 |
Baseline characteristics
| Characteristic | Study Group |
|---|---|
| Age, Continuous | 23.5 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 33 |
| other Total, other adverse events | 0 / 33 | 0 / 33 |
| serious Total, serious adverse events | 0 / 33 | 0 / 33 |
Outcome results
Primary
CYP2D6 Activity as Measured by the Molar Concentration Ratio of Dextromethorphan (DM)/Dextrophan (DX)
dextromethorphan (DM)/dextrophan (DX) molar concentration Metabolic Ratio. The metabolic ratio is unit-less as the molar concentrations cancel out.
Time frame: 1 week to 6 months
Population: The number of subjects included in the analysis is less than the number that completed the study because only cytochrome P450 extensive metabolizers were included in the analysis. Each person served as their own control (pre-isotretinoin and with isotretinoin). Pre-isotretinoin study was completed prior to starting isotretinoin and then the same study was completed after the subject had been on isotretinoin for 1 week to 6 months.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Pre-isotretinoin | CYP2D6 Activity as Measured by the Molar Concentration Ratio of Dextromethorphan (DM)/Dextrophan (DX) | 16.0 Ratio |
| With Isotretinoin | CYP2D6 Activity as Measured by the Molar Concentration Ratio of Dextromethorphan (DM)/Dextrophan (DX) | 12.5 Ratio |