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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-020617-82 | EudraCT Number |
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Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. After oral administration, tramadol is rapidly and almost completely absorbed. Tramadol is extensively metabolised by O- and N-demethylation, which are catalysed by the liver CYP-450 enzymes. O-desmethyltramadol is an active metabolite and its formation is catalysed by CYP2D6. The formation of inactive metabolites is catalysed by CYP3A4 and 2B6. This study is aimed to investigate the possible interaction of oral tramadol with itraconazole and ticlopidine, which are inhibitors of CYP3A4 and 2B6. Twelve healthy male or female adult non-smoking volunteers aged 18-40 years with body weights within ±15% of the ideal weight for height are taken into the study. Primary endpoints of the study are plasma concentrations of tramadol and its metabolites.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Ticlopidine | Active Comparator |
| |
| Ticlopidine and itraconazole | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | The subjects will be given orally placebo twice a day for 5 days prior to the study. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of tramadol and its metabolites in plasma | 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours after administration of tramadol |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolites of tramadol in urine | Urine will be collected for 24 hours and M1 and M2 metabolites of tramadol are quantified from 0-12h and 12-24h fractions | 0-12 and 12-24 hour fractions after administration of tramadol |
| Serotonin concentrations |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Klaus T Olkkola, MD, PhD, Prof | Turku University Hospital and Turku University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital | Turku | 20521 | Finland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23099620 | Derived | Hagelberg NM, Saarikoski T, Saari TI, Neuvonen M, Neuvonen PJ, Turpeinen M, Scheinin M, Laine K, Olkkola KT. Ticlopidine inhibits both O-demethylation and renal clearance of tramadol, increasing the exposure to it, but itraconazole has no marked effect on the ticlopidine-tramadol interaction. Eur J Clin Pharmacol. 2013 Apr;69(4):867-75. doi: 10.1007/s00228-012-1433-0. Epub 2012 Oct 26. |
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| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Ticlopidine | Drug | The subjects will be given orally ticlopidine 250mg twice a day for 5 days prior to the study. |
|
| Ticlopidine and itraconazole | Drug | The subjects will be given orally ticlopidine 250mg twice a day and itraconazole 200mg as a single daily dose for 5 days prior to the study. |
|
Serotonin concentrations will be analyzed with chromatographical methods from the blood samples drawn 0, 4 and 8 hours after tramadol administration
| 0, 4 and 8 hours after tramadol administration |
| Pharmacodynamic effects | The psychomotor effects of tramadol will be assessed with the measurement of pupil size with Cogan's pupillometer, Maddox wing test and digit symbol substitution test | 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after administration of tramadol |
| Analgesia | The analgesic effect of tramadol will be evaluated using the cold pressor test. Briefly, the subject's hand is immersed into ice-cold water of + 4° C up to the wrist. The subject is told to keep his or her hand in the water and to report when the cold sensation becomes painful. Cold pain threshold is defined as the latency from the immersion of the hand to the subject's first report of pain. Cold pain intensity is assessed at 30 s intervals following immersion of the hand in cold water for up to 60s . A verbal numerical rating scale of 0-100 will be used. | 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of tramadol |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014230 | Triazoles |
| D001393 | Azoles |
| D010879 | Piperazines |