title: Pharmacokinetics, bioavailability, and hemodynamic effects of trazodone after intravenous and oral administration of a single dose to dogs.
abstract: OBJECTIVE
  To determine the pharmacokinetics and hemodynamic effects of trazodone after IV and oral administration in dogs and bioavailability after oral administration.
  
  
  METHODS
  6 adult Beagles.
  
  
  METHODS
  Dogs received trazodone HCl (8 mg/kg) orally and IV in a randomized controlled crossover design. Blood samples were collected at various times after administration. Heart rates and indirectly measured blood pressures of dogs and plasma concentrations and pharmacokinetics of trazodone were determined.
  
  
  RESULTS
  Following IV administration, the mean ± SD elimination half-life, apparent volume of distribution, and plasma total body clearance were 169 ± 53 minutes, 2.53 ± 0.47 L/kg, and 11.15 ± 3.56 mL/min/kg, respectively. Following oral administration, the mean ± SD elimination half-life and absolute bioavailability were 166 ± 47 minutes and 84.6 ± 13.2%, respectively. Maximum plasma concentration following oral administration was 1.3 ± 0.5 μ/mL, and time to maximum plasma concentration was 445 ± 271 minutes. After IV administration, all dogs immediately developed transient tachycardia (184.3 ± 8.0 beats/min), and 3 of 6 dogs developed aggression. Increase in heart rate was significantly associated with increase in plasma drug concentration following IV administration.
  
  
  CONCLUSIONS
  Results of this study indicated oral administration of trazodone resulted in acceptable absolute bioavailability, with substantial variability in time to maximum plasma concentration. Individualized approaches in dosing intervals may be necessary for dogs receiving oral trazodone. An orally administered dose of 8 mg/kg was well tolerated in dogs; IV administration of a dose of 8 mg/kg caused substantial adverse effects, including tachycardia and behavior disinhibition.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
authors.forename: Ariane R
authors.initials: AR
authors.lastname: Jay
authors.forename: Ursula
authors.initials: U
authors.lastname: Krotscheck
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Parsley
authors.forename: Lisa
authors.initials: L
authors.lastname: Benson
authors.forename: Ariel
authors.initials: A
authors.lastname: Kravitz
authors.forename: Abby
authors.initials: A
authors.lastname: Mulligan
authors.forename: Jharon
authors.initials: J
authors.lastname: Silva
authors.forename: Hussni
authors.initials: H
authors.lastname: Mohammed
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Schwark
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D006207:Half-Life; D006439:Hemodynamics; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D014196:Trazodone / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D014151:Anti-Anxiety Agents; D014196:Trazodone