Effect of Duloxetine and Venlafaxine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol: A Three-phase Randomized Balanced Cross-over Study in Healthy Volunteers
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. This study is aimed to investigate the possible interaction of oral tramadol with duloxetine and venlafaxine. Duloxetine is known to inhibit CYP2D6. 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
- Concentration of tramadol and its metabolites in plasma [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours after administration of tramadol ] [ Designated as safety issue: No ]
- Serotonin concentrations [ Time Frame: 0, 4 and 8 hours after tramadol administration ] [ Designated as safety issue: No ]Serotonin concentrations will be analyzed with chromatographical methods from the blood samples drawn 0, 4 and 8 hours after tramadol administration
- Pharmacodynamic effects [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after administration of tramadol ] [ Designated as safety issue: No ]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
- Analgesia [ Time Frame: 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after the administration of tramadol ] [ Designated as safety issue: No ]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.
|Study Start Date:||October 2011|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
The subjects will be given orally placebo twice a day for 8 days prior to the study.
|Active Comparator: Duloxetine||
The subjects will be given orally duloxetine 30mg twice a day for 8 days prior to the study.
|Active Comparator: Venlafaxine||
The subjects will be given orally venlafaxine 37,5mg twice a day for 8 days prior to the study.