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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
PMID:6132969
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)。

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