Cytochrome P450 CYP2D6 Enzyme Deficiency, Drug Effect, Drug Intolerance
Conditions
Keywords
children, pain, Cytochrome P450 CYP2D6 genotype, Cytochrome P450 CYP2D6 phenotype, Pupillometry
Brief summary
Pupillometry will be performed before administration of tramadol, at T0 and then 1 to twice per hour in children having received tramadol as a pain killer as part of his/her routine care. Pupillometry measurement will be correlate to CYP2D6 phenotype and CYP2D6 genetic score
Detailed description
The proposed study is a single-center, observational and prospective study which will be conducted at the Pediatric Emergency Department, Geneva Children's Hospital. This study will begin in January 2016 and will last one year. 53 patients are planned to be enrolled. Children receiving oral tramadol as a pain killer at the emergency department, as part of their routine care, will be informed of the current study. Patients willing to participate will be included in the study after signing the inform consent (or respectively his/her parents or legal guardians). A unique oral dose of dextromethorphan (0.15 mg/kg) will be given to the participant for CYP2D6 phenotyping (T0). Two hours later, capillary whole blood will be sampled to 1) measure the metabolic ratio dextrorphan/dextromethorphan (MRDOR/DEM) in order to determine CYP2D6 phenotype (validated metrics for CYP2D6 phenotyping), 2) measure tramadol and its active metabolite O-desmethyltramadol (M1), and 3) to genotype for CYP2D6. Saliva sample will also be performed to genotype for CYP2D6. Pupillometry will be performed before administration of tramadol, at T0 and then 1 to twice per hour, throughout the patient's stay at the emergency department.
Interventions
DEVICEPupillometry
Pupillometry performed before administration of tramadol, at T0 and then 1 to twice per hour, during the stay of the patient in the emergency department
Sponsors
University Hospital, Geneva
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Age 1-15 year at time of inclusion * Weight ≥ 10 kg * Treatment with tramadol as a pain killer administrated as part of their routine care * Parent/Legal guardian has been informed about the study and has signed Informed Consent Form
Exclusion criteria
* Known kidney or liver disease * Concomitant treatment with inhibitors/inducers of CYP2D6 and CYP3A * Documented previous adverse reaction to tramadol or dextromethorphan * Concomitant treatment with any opiate drug and/or any drug with a known impact on pupil size * Any concomitant condition, which in the opinion of the investigator would preclude a subject's participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pupillometry parameters and CYP2D6 phenotype | 0-6hours after tramadol administration | Correlation between pupillometry parameters and CYP2D6 phenotype |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pupillometry parameters and CYP2D6 genotype | 0-6hours after tramadol administration | Correlation between pupillometry parameters and CYP2D6 genotype |
| pupillometry parameters and tramadol concentration | 0-6hours after tramadol administration | Correlation between pupillometry parameters and blood levels of tramadol and its active metabolite M1 |
Countries
Switzerland
Outcome results
None listed