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异丙肾上腺素在人和犬体内经气雾剂及直接支气管内给药后的代谢情况。

Metabolism of isoprenaline after aerosol and direct intrabronchial administration in man and dog.

作者信息

Blackwell E W, Briant R H, Conolly M E, Davies D S, Dollery C T

出版信息

Br J Pharmacol. 1974 Apr;50(4):587-91. doi: 10.1111/j.1476-5381.1974.tb08593.x.

DOI:10.1111/j.1476-5381.1974.tb08593.x
PMID:4447860
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1776727/
Abstract

1 Administration of isoprenaline by aerosol inhalation to man results in over 80% being metabolized to the sulphate conjugate.2 The majority of an inhaled dose is probably swallowed since the metabolic pattern resembles that after an oral dose.3 Isoprenaline, administered in aqueous solution directly into the bronchial tree in both man and dog, is rapidly O-methylated to 3-O-methyl isoprenaline, which is subsequently conjugated with sulphate.4 3-O-Methylation is the main metabolic pathway for the small part of an inhaled dose which does enter the bronchial tree.

摘要
  1. 对人体进行异丙肾上腺素气雾剂吸入给药后,超过80%的药物会代谢为硫酸酯共轭物。

  2. 吸入剂量的大部分可能会被吞咽,因为其代谢模式与口服给药后相似。

  3. 在人和狗身上,将异丙肾上腺素以水溶液形式直接注入支气管树后,它会迅速O-甲基化生成3-O-甲基异丙肾上腺素,随后与硫酸盐结合。

  4. 3-O-甲基化是吸入剂量中进入支气管树的一小部分药物的主要代谢途径。

相似文献

1
Metabolism of isoprenaline after aerosol and direct intrabronchial administration in man and dog.异丙肾上腺素在人和犬体内经气雾剂及直接支气管内给药后的代谢情况。
Br J Pharmacol. 1974 Apr;50(4):587-91. doi: 10.1111/j.1476-5381.1974.tb08593.x.
2
Metabolism of isoprenaline in dog and man.异丙肾上腺素在犬类和人类体内的代谢。
Br J Pharmacol. 1972 Nov;46(3):458-72. doi: 10.1111/j.1476-5381.1972.tb08143.x.
3
Metabolism of isoprenaline and other bronchodilator drugs in man and dog.异丙肾上腺素及其他支气管扩张药在人和犬体内的代谢
Bull Physiopathol Respir (Nancy). 1972 May-Jun;8(3):679-83.
4
Reversed-phase high-performance liquid chromatography and amperometric detection of 3-O-methyl isoprenaline sulphate: application to studies on the presystemic metabolism of d-isoprenaline in man.反相高效液相色谱法及安培检测法测定硫酸3 - O - 甲基异丙肾上腺素:应用于人体中d - 异丙肾上腺素的首过代谢研究
J Chromatogr. 1985 Feb 8;337(2):311-20. doi: 10.1016/0378-4347(85)80044-x.
5
Sulphate conjugation of isoprenaline by lung, small intestine and other organs.肺、小肠及其他器官对异丙肾上腺素的硫酸结合作用。
Biochem Pharmacol. 1982 Jan 1;31(1):59-62. doi: 10.1016/0006-2952(82)90236-2.
6
Isolated perfused rabbit lung as a model for intravascular and intrabronchial administration of bronchodilator drugs I:Isoproterenol.离体灌注兔肺作为支气管扩张药物血管内和支气管内给药的模型I:异丙肾上腺素
J Pharm Sci. 1982 Nov;71(11):1268-74. doi: 10.1002/jps.2600711121.
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The quantitative assessment of isoprenaline metabolism in man.人体中异丙肾上腺素代谢的定量评估。
Clin Chim Acta. 1969 Dec;26(3):381-6. doi: 10.1016/0009-8981(69)90062-x.
8
Isolated perfused rabbit lung as a model for intravascular and intrabronchial administration of bronchodilator drugs II:Isoproterenol prodrugs.离体灌注兔肺作为支气管扩张药物血管内和支气管内给药的模型II:异丙肾上腺素前药
J Pharm Sci. 1982 Nov;71(11):1274-81. doi: 10.1002/jps.2600711122.
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The metabolic fate of DL(7-3H)isoprenaline in man and dog.DL(7-³H)异丙肾上腺素在人和狗体内的代谢归宿。
Biochem J. 1969 Aug;114(1):8P. doi: 10.1042/bj1140008pa.
10
Lack of cardiac or bronchodilator tachyphylaxis to isoprenaline in the dog.犬对异丙肾上腺素不存在心脏或支气管扩张剂快速耐受性。
Br J Pharmacol. 1975 Mar;53(3):333-40. doi: 10.1111/j.1476-5381.1975.tb07368.x.

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Br J Clin Pharmacol. 1976 Aug;3(4):583-9. doi: 10.1111/j.1365-2125.1976.tb04879.x.
2
Treatment of severe anaphylactic reactions to insect stings.昆虫叮咬所致严重过敏反应的治疗。
J R Soc Med. 1981 Aug;74(8):567-9. doi: 10.1177/014107688107400801.
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Catecholamine transport in isolated lung parenchyma of pig.猪离体肺实质中的儿茶酚胺转运
Br J Pharmacol. 1982 Aug;76(4):507-13. doi: 10.1111/j.1476-5381.1982.tb09247.x.
4
Measurement of bronchial reactivity: a question of interpretation.支气管反应性的测量:一个解释的问题。
Thorax. 1981 Aug;36(8):561-5. doi: 10.1136/thx.36.8.561.
5
Effect of an extension tube on the bronchodilator efficacy of terbutaline delivered from a metered dose inhaler.延长管对定量吸入器递送的特布他林支气管扩张疗效的影响。
Thorax. 1980 Jul;35(7):552-6. doi: 10.1136/thx.35.7.552.
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First-pass elimination. Basic concepts and clinical consequences.首过消除。基本概念及临床后果。
Clin Pharmacokinet. 1984 Jan-Feb;9(1):1-25. doi: 10.2165/00003088-198409010-00001.
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Comparison between the effects of inhaled isoprenaline and fenoterol on plasma cyclic AMP and heart rate in normal subjects.吸入异丙肾上腺素与非诺特罗对正常受试者血浆环磷腺苷及心率影响的比较。
Br J Clin Pharmacol. 1984 Feb;17(2):165-70. doi: 10.1111/j.1365-2125.1984.tb02332.x.
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Dosage and delivery of nebulised beta agonists in hospital.医院中雾化吸入β受体激动剂的剂量与给药方式
Thorax. 1983 Oct;38(10):751-4. doi: 10.1136/thx.38.10.751.
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Comparison of hypokalaemic, electrocardiographic and haemodynamic responses to inhaled isoprenaline and salbutamol in young and elderly subjects.年轻和老年受试者吸入异丙肾上腺素和沙丁胺醇后低钾血症、心电图及血流动力学反应的比较。
Eur J Clin Pharmacol. 1991;40(3):255-60. doi: 10.1007/BF00315205.
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Clin Pharmacokinet. 1990 Apr;18(4):270-94. doi: 10.2165/00003088-199018040-00002.

本文引用的文献

1
Metanephrine and normetanephrine in human urine: method and results.人尿中的变肾上腺素和去甲变肾上腺素:方法与结果
J Lab Clin Med. 1962 Aug;60:212-23.
2
Metabolism of epinephrine and other sympathomimetic amines.肾上腺素及其他拟交感神经胺的代谢
Physiol Rev. 1959 Oct;39:751-76. doi: 10.1152/physrev.1959.39.4.751.
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The chemical estimation of adrenaline-like substances in blood.血液中肾上腺素样物质的化学测定。
Biochem J. 1952 Jun;51(3):311-8. doi: 10.1042/bj0510311.
4
Separation of catecholamines and metanephrine and normetanephrine using a weak cation-exchange resin.使用弱阳离子交换树脂分离儿茶酚胺、变肾上腺素和去甲变肾上腺素。
Anal Biochem. 1965 Jun;11(3):575-9. doi: 10.1016/0003-2697(65)90075-8.
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Methyltransferase enzymes in red blood cells.红细胞中的甲基转移酶
J Pharmacol Exp Ther. 1971 Mar;176(3):650-4.
6
Metabolism of isoprenaline in dog and man.异丙肾上腺素在犬类和人类体内的代谢。
Br J Pharmacol. 1972 Nov;46(3):458-72. doi: 10.1111/j.1476-5381.1972.tb08143.x.
7
On the occurrence of phenol and steroid sulphokinases in the human gastrointestinal tract.关于人胃肠道中酚和类固醇硫酸激酶的存在情况。
Scand J Gastroenterol. 1968;3(4):369-75. doi: 10.3109/00365526809180131.
8
The metabolism of sympathomimetic bronchodilator drugs by the isolated perfused dog lung.拟交感神经支气管扩张药在离体灌注犬肺中的代谢。
Xenobiotica. 1973 Dec;3(12):787-99. doi: 10.3109/00498257309151603.