title: The influence of a single and chronic administration of venlafaxine on tramadol pharmacokinetics in a rabbit model.
abstract: 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 100mg of tramadol per os (one slow release tablet) and 75mg of venlafaxine (one prolonged release capsule), and were divided into four groups: control group - a single dose of tramadol alone, 1day group - a single dose of tramadol and venlafaxine, 7 and 14days 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 14days resulted in faster elimination of tramadol compared to the control group: significantly higher values of kel, and lower values of t1/2keland MRT for the 7 and 14days group were observed. Although no differences in bioavailability of tramadol were obtained.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: d.szkutnik@wp.pl.
authors.forename: Danuta
authors.initials: D
authors.lastname: Szkutnik-Fiedler
authors.affiliation: Polpharma Biologics, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Balcerkiewicz
authors.affiliation: Department of Computer Sciences and Statistics, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Irina
authors.initials: I
authors.lastname: Pilipczuk
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Wyrowski
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Urjasz
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D008297:Male; D011817:Rabbits; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013607:Tablets; D014147:Tramadol / Q000493:pharmacokinetics*; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D002214:Capsules; D003692:Delayed-Action Preparations; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D013607:Tablets; D014147:Tramadol; D000069470:Venlafaxine Hydrochloride
keywords: Pharmacokinetic interactions; Rabbits; Serotonin syndrome; Tramadol; Venlafaxine