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

Background 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. methods 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. results 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 el,and lower values of t1/2kel and mrt for the 7 and 14 days group were observed. although no differences in bioavailability of tramadol were obtained. conclusion 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. © 2017 institute of pharmacology,polish academy of sciences