title: Pharmacokinetics of mirtazapine and its main metabolites in Beagle dogs: a pilot study.
abstract: Mirtazapine (MRT) is a human antidepressant drug mainly metabolised by the cytochrome P450 enzyme system to 8-OH mirtazapine (8-OH) and dimetilmirtazapine (DMR). The drug is usually administered to dogs with anorexia according to doses extrapolated from humans, although it could also have applications as an antidepressant and analgesic in this species. The aim of this study was to assess the pharmacokinetics of MRT and its metabolites, DMT and 8-OH. Six healthy male Beagle dogs were administered MRT orally (20 mg/dog) and plasma MRT and metabolite concentrations were evaluated by high performance liquid chromatography with fluorescence detection. The pharmacokinetic profiles of MRT and DMR were similar (detected from 0.25 up to 10 h), while 8-OH (detected from 0.50 up to 10 h) attained the highest concentrations. The mean half-life of MRT was 6.17 h with a clearance of 1193 mL/h/kg. The study showed that MRT has a different pharmacokinetic profile in the dog compared to other species.
authors.affiliation: Department of Veterinary Clinics, Veterinary Teaching Hospital, University of Pisa, Via Livornese (lato monte) 1, San Piero a Grado, 56122 Pisa, Italy. mgiorgi@vet.unipi.it
authors.forename: Mario
authors.initials: M
authors.lastname: Giorgi
authors.forename: Hyoin
authors.initials: H
authors.lastname: Yun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D004285:Dogs / Q000378:metabolism; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000078785:Mirtazapine; D010865:Pilot Projects
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine; C415843:8-hydroxymirtazapine; C119256:demethylmirtazapine