Pharmacokinetics and behavioural effects of a single oral dose of trazodone in rabbits.

Abstract

Objective: To evaluate the pharmacokinetics and pharmacodynamics of a single oral dose of trazodone in laboratory rabbits.

Study design: Randomised, blinded, Latin-square study.

Animals: A group of eight healthy, juvenile, female New Zealand White rabbits.

Methods: Auricular venous catheters were placed in six rabbits before oral trazodone (20 mg kg^-1) administration. Blood was sampled immediately before and at 15 and 30 minutes and 1, 2, 4, 8, 12, 18 and 24 hours after treatment. Trazodone plasma concentrations were determined using high-performance liquid chromatography-mass spectrometry. A group of eight rabbits were equipped with accelerometers (activity) and video recorded. They randomly received one of three treatments: oral trazodone (20 mg kg^-1; TRAZ), placebo (corn oil base; PLAC) or no treatment (CONTR) with a 3 day washout period between treatments. Exploring, grooming, resting, vigilance, hiding and ingesting behaviours were evaluated for 10 hours (0-2, 2-4, 4-6, 6-8 and 8-10 hours).

Results: Mean maximum plasma concentration, 6592.6 ± 586.5 ng mL^-1, was 0.3 ± 0.11 hours after treatment. Mean half-life was 3.24 ± 0.36 hours and area under the curve from zero to infinity 25,412.5 ± 5420.9 ng mL^-1 hour^-1. Activity was higher in TRAZ and PLAC than CONTR at 0-2 hours, with TRAZ exploring more. Hiding was reduced in TRAZ versus CONTR (0-2 hours and 4-6 hours) and versus PLAC (0-6 hours). Resting increased in TRAZ versus PLAC (2-4 hours) and CONTR (4-6 hours); PLAC rested less at 2-4 hours than at 8-10 hours. Vigilance tended to be lower in TRAZ versus CONTR. Food intake decreased in TRAZ at 2-4 hours. Grooming varied over time.

Conclusions and clinical relevance: Trazodone-treated animals showed reduced activity, less hiding and more resting than PLAC and decreased food intake 2-4 hours post-treatment.