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. Findings: 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.

PHARMACOKINETICS OF MIRTAZAPINE AND ITS MAIN METABOLITES AFTER SINGLE INTRAVENOUS AND ORAL ADMINISTRATIONS IN RATS AT TWO DOSE RATES

GIORGI, MARIO
2014

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. Findings: 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.
Rouini, M. R.; Lavasani, H.; Sheikholeslami, B.; Owen, H.; Giorgi, Mario
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/281540
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