R-(-)-间羟去甲肾上腺素的哺乳动物代谢

The mammalian metabolism of R-(-)-m-synephrine.

作者信息

Ibrahim K E, Midgley J M, Crowley J R, Williams C M

出版信息

J Pharm Pharmacol. 1983 Mar;35(3):144-7. doi: 10.1111/j.2042-7158.1983.tb04293.x.

DOI:10.1111/j.2042-7158.1983.tb04293.x

Abstract

The metabolism of R-(-)-m-synephrine (administered orally and by inhalation in man and intraperitoneally in rats) was studied quantitatively by a gas chromatography-mass spectrometry-selected ion monitoring (g.c.-m.s.-s.i.m.) method using deuterated internal standards. When m-synephrine hydrochloride was administered orally to humans in normal dosage regimens four main metabolites were excreted in urine: (i) unconjugated m-hydroxymandelic acid (MHMA, 30%), (ii) m-hydroxyphenylglycol (MHPG) sulphate (6%), (iii) m-synephrine sulphate (47%) and (iv) m-synephrine glucuronide (12%). The comparable figures after inhalation of the drug were 24, 6, 56 and 5%. Intraperitoneal injection of m-synephrine into rats gave: unconjugated MHMA (5%), MHPG sulphate (35%), unconjugated m-synephrine (7%) and conjugates of m-synephrine (9%:4% as the glucuronide and 5% as the sulphate).

摘要

采用气相色谱-质谱联用选择离子监测（g.c.-m.s.-s.i.m.）法并使用氘代内标物，对R-(-)-间羟去甲肾上腺素（在人体中口服和吸入给药，在大鼠中腹腔注射给药）的代谢情况进行了定量研究。当以正常剂量方案给人体口服盐酸间羟去甲肾上腺素时，尿液中排泄出四种主要代谢物：（i）未结合的间羟基扁桃酸（MHMA，30%），（ii）间羟基苯乙二醇（MHPG）硫酸盐（6%），（iii）间羟去甲肾上腺素硫酸盐（47%）和（iv）间羟去甲肾上腺素葡糖醛酸苷（12%）。吸入该药物后对应的数字分别为24%、6%、56%和5%。给大鼠腹腔注射间羟去甲肾上腺素后得到：未结合的MHMA（5%）、MHPG硫酸盐（35%）、未结合的间羟去甲肾上腺素（7%）和间羟去甲肾上腺素的结合物（9%：4%为葡糖醛酸苷，5%为硫酸盐）。