title: Pharmacokinetics of mirtazapine and its main metabolites after single intravenous and oral administrations in rats at two dose rates.
abstract: BACKGROUND
  Mirtazapine (MRZ) is a human antidepressant drug metabolized to 8-OH mirtazapine (8-OH) and dimethylmirtazapine (DMR) metabolites. Recently, this drug has been proposed as a potential analgesic for use in a multidrug analgesic regime in the context of veterinary medicine. The aim of this study was to assess the pharmacokinetics of MRZ and its metabolites DMR and 8-OH in rats.
  
  
  RESULTS
  Eighteen fasted, healthy male rats were randomly divided into 3 groups (n = 6). Animals in these groups were respectively administered MRZ at 2 and 10 mg/kg orally and 2 mg/kg intravenously. Plasma MRZ and metabolite concentrations were evaluated by HPLC-FL detection method. After intravenous administration, MRZ was detected in all subjects, while DMR was only detected in three. 8-OH was not detected. After oral administration, MRZ was detected in 3 out of 6 rats treated with 2 mg/kg, it was detected in 6 out of 6 animals in the 10 mg/kg group. DMR was only detectable in the latter group, while 8-OH was not detected in either group. The oral bioavailability was about 7% in both groups.
  
  
  CONCLUSIONS
  The plasma concentration of the MRZ metabolite 8-OH was undetectable, and the oral bioavailability of the parental drug was very low.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Rouini
authors.forename: Hoda
authors.initials: H
authors.lastname: Lavasani
authors.forename: Behjat
authors.initials: B
authors.lastname: Sheikholeslami
authors.forename: Helen
authors.initials: H
authors.lastname: Owen
authors.affiliation: Department of Veterinary Sciences, Veterinary Teaching Hospital, University of Pisa, Via Livornese (lato monte), San Piero a Grado, 56122 Pisa, Italy. mgiorgi@vet.unipi.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Giorgi