Post-operative Patients Treated by Tramadol Clinical Trial
— CYTRAMOfficial title:
Validation of a New Method to Detect CYP2D6 Poor Metabolizers by Monitoring Seric Concentrations of O-demethyl-tramadol and Tramadol to Make a Ratio in Comparison With Genotyping in Post-operative Patients Treated With Intravenous Tramadol
Many methods to detect CYP2D6 poor metabolizers have been validated. Some of them are based
on phenotyping (metabolism of dextromethorphan or debrisoquine) and some others on
genotyping. Up to now, CYP2D6 pharmacogenetics has been restricted to the field of research,
in spite of poor metabolizer profile concerns 5 to 10 % of caucasian population.
Nevertheless, the polymorphism of CYP2D6 is responsible for the metabolism of many drugs,
particularly of two opioids involved in pain management: codeine and tramadol, their
metabolites representing the most effective part of the drug effect. So prescribing codeine
or tramadol in a patient poor metabolizer for the CYP2D6 is likely to be ineffective in pain
management.
O-demethyl-tramadol, the metabolite of tramadol via CYP2D6, is important to consider because
its analgesic effect is 2 to 4 times more potent than tramadol.
The investigators propose to phenotype CYP2D6 in post-operative patients treated by tramadol
by monitoring seric concentrations of O-demethyl tramadol and tramadol to make a ratio in
comparison with genotype, and to find a threshold to determine poor metabolizers. As already
described, genotyping CYP2D6 will use a rapid detection method of the alleles implicated in
poor metabolizer status (CYP2D6*3, *4, *5 et *6) in a Caucasian population. Sampling will be
executed at two times (H24 and H48 after surgery) and only with blood (three EDTA tubes)
during the post-operative monitoring of the patients. This study is likely to include 320
post-operative patients treated with intravenous tramadol during one year in three
university hospitals centers (CHU of Caen, Creteil and Rouen).
The first aim of this study is the validation of monitoring seric concentrations of
O-demethyl-tramadol and tramadol to make the ratio in order to detect CYP2D6 poor
metabolizers in therapeutic situation, comparing the result with genotyping. The finding of
a poor metabolizer status in a patient will make the choice of analgesic drugs easier,
avoiding tramadol and codeine. The final objective of this research is to be able to
determine the CYP2D6 phenotype in a patient treated by tramadol without a good analgesia. By
a single take of blood and a rapid response, this method should be liked to improve pain
management. Furthermore, CYP2D6 phenotyping is interesting for the patient because many
other drugs depend on this way of metabolism.
| Status | Completed |
| Enrollment | 301 |
| Est. completion date | June 2011 |
| Est. primary completion date | June 2011 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - age > 18 years, post-operative patient treated with intravenous tramadol - Caucasian origin - take of blood at H24 and H48 in the post-operative monitoring Exclusion Criteria: - patient having already been included in the study - patient taking opioid drugs before surgery - patient taking one or more drugs inhibiting the CYP2D6 before or during surgery - pregnancy or breast feeding patients having one or more contraindications for taking tramadol in post-operative analgesia - hepatocellular incapacity (TP < 70%) |
Observational Model: Cohort, Time Perspective: Prospective
| Country | Name | City | State |
|---|---|---|---|
| France | Caen University Hospital | Caen | |
| France | Private Clinic Saint-Martin | Caen | |
| France | Créteil University Hospital | Créteil | |
| France | Rouen University Hospital | Rouen |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Caen |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | To phenotype CYP2D6 in post-operative patients treated by tramadol by monitoring seric concentrations of O-demethyl tramadol and tramadol to make a ratio in comparison with genotype, and to find a threshold to determine poor metabolizers. | H24 and H48 after surgery | No |