Department of Veterinary Sciences, Veterinary Teaching Hospital, University of Pisa, Via Livornese (lato monte), San Piero a Grado, 56122 Pisa, Italy.
Daru. 2014 Jan 7;22(1):13. doi: 10.1186/2008-2231-22-13.
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.
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.
The plasma concentration of the MRZ metabolite 8-OH was undetectable, and the oral bioavailability of the parental drug was very low.
米氮平（MRZ）是一种人类抗抑郁药，代谢为 8-OH 米氮平（8-OH）和二甲米氮平（DMR）代谢物。最近，这种药物已被提议作为兽医多药物镇痛方案中的一种潜在镇痛药。本研究旨在评估 MRZ 及其代谢物 DMR 和 8-OH 在大鼠中的药代动力学。
18 只禁食的健康雄性大鼠被随机分为 3 组（每组 6 只）。这些组的动物分别以 2 和 10mg/kg 口服和 2mg/kg 静脉内给予 MRZ。通过 HPLC-FL 检测法评估血浆 MRZ 和代谢物浓度。静脉给药后，所有受试者均检测到 MRZ，而仅在 3 例中检测到 DMR。未检测到 8-OH。口服给药后，在 2mg/kg 组的 6 只动物中的 3 只中检测到 MRZ，在 10mg/kg 组的 6 只动物中均检测到 MRZ。仅在后一组中可检测到 DMR，而在两组中均未检测到 8-OH。两组的口服生物利用度均约为 7%。
母体药物的血浆浓度 8-OH 代谢物不可检测，口服生物利用度非常低。
