猪体内非莫西汀的肝脏消除

Hepatic elimination of femoxetine in pig.

作者信息

Bechgaard E, Keiding S, Lund J, Christiansen L A

出版信息

Acta Pharmacol Toxicol (Copenh). 1983 Jan;52(1):1-7. doi: 10.1111/j.1600-0773.1983.tb01067.x.

DOI:10.1111/j.1600-0773.1983.tb01067.x

Abstract

Hepatic elimination of femoxetine was studied in seven anaesthetized 40 kg pigs by means of constant rate infusions of 3-41 mg/min. (8.6-118 mumol/min.) into the portal vein. The elimination followed saturation kinetics (Michaëlis-Menten constants: Vmax 12 mg . min.-1 . kg-1 liver; Km 1.3 mg . 1-1 blood) and was characterised by high hepatic extraction, due to metabolism. The hepatic output of the active metabolite, nor-femoxetine, was very low, indicating that other metabolic pathways than demethylation were more important in the pig. The high hepatic elimination in the pig corresponds to the high first pass effect, earlier found in man, and it depends upon the infusion rate as well as the total dose.

摘要

通过以3 - 41毫克/分钟（8.6 - 118微摩尔/分钟）的恒定速率向门静脉输注，在7只体重40千克的麻醉猪身上研究了非莫西汀的肝脏清除情况。清除遵循饱和动力学（米氏常数：最大反应速度为12毫克·分钟⁻¹·千克⁻¹肝脏；米氏常数为1.3毫克·升⁻¹血液），并且由于代谢作用，其特征为肝脏高提取率。活性代谢物去甲非莫西汀的肝脏输出非常低，这表明在猪体内，除去甲基化之外的其他代谢途径更为重要。猪体内的高肝脏清除率与在人类中较早发现的高首过效应相对应，并且它取决于输注速率以及总剂量。