The influence of a single and chronic administration of venlafaxine on tramadol pharmacokinetics in a rabbit model

• Published in: Pharmacological reports Vol. 69; no. 3; p. 555
• Main Authors: Szkutnik-Fiedler, Danuta, Grabowski, Tomasz, Balcerkiewicz, Monika, Michalak, Michał, Pilipczuk, Irina, Wyrowski, Łukasz, Urjasz, Hanna, Grześkowiak, Edmund
• Format: Journal Article
• Language: English
• Published: Switzerland 01.05.2017
• Subjects: Pharmacokinetic interactions; Rabbits; Serotonin syndrome; Tramadol; Venlafaxine
• ISSN: 1734-1140

The combined use of tramadol with selective serotonin and norepinephrine reuptake inhibitors e.g. venlafaxine may be associated with serotonin syndrome. No previous studies exist examining the influence of a weak CYP2D6 inhibitor venlafaxine on the pharmacokinetics of tramadol. Therefore, the aim of this study was to determine the effect of a single and chronic administration of venlafaxine on the pharmacokinetics of tramadol using a rabbit model. Adult New Zealand white rabbits of both sexes (n = 21) were used. Animals received 100 mg of tramadol per os (one slow release tablet) and 75 mg of venlafaxine (one prolonged release capsule), and were divided into four groups: control group - a single dose of tramadol alone, 1 day group - a single dose of tramadol and venlafaxine, 7 and 14 days groups - seven and fourteen days administration of venlafaxine once daily plus a single dose of tramadol on the last day of the study. Venlafaxine administration over a period of 7 and 14 days resulted in faster elimination of tramadol compared to the control group: significantly higher values of k , and lower values of t and MRT for the 7 and 14 days group were observed. Although no differences in bioavailability of tramadol were obtained. Using a rabbit model, there is no evidence that the combined administration of tramadol and venlafaxine may increase the plasma exposure of tramadol and therefore increase the risk of serotonin syndrome.