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用高灵敏度气相色谱-质谱法测定大鼠、犬和人体中普罗帕酮的血浆蛋白结合率。

Determination of plasma protein binding of propafenone in rats, dogs and humans by highly sensitive gas chromatography-mass spectrometry.

作者信息

Higuchi S, Urano C, Kawamura S

出版信息

J Chromatogr. 1985 Jun 14;341(2):305-11. doi: 10.1016/s0378-4347(00)84044-x.

DOI:10.1016/s0378-4347(00)84044-x
PMID:2863278
Abstract

A highly sensitive method for the determination of propafenone in plasma has been established using gas chromatography-mass spectrometry with the deuterium-labelled compound as an internal standard. Plasma levels as low as 1 ng/ml were measured using 0.5-ml plasma samples. Plasma protein binding of the drug in rats, dogs and humans in vitro and in vivo was determined by the proposed method. About 90% of the drug was bound to the plasma protein in all species in vitro (20-500 ng/ml) and 69-88% in rats, 90-95% in dogs and 77-89% in humans after oral administration of the drug at doses of 50 mg/kg, 5 mg/kg and 200 mg per person, respectively.

摘要

已建立一种高灵敏度的血浆中普罗帕酮测定方法,该方法采用气相色谱 - 质谱联用,以氘标记化合物作为内标。使用0.5毫升血浆样本可测定低至1纳克/毫升的血浆水平。通过该方法测定了该药物在大鼠、犬和人体的体外及体内血浆蛋白结合率。在体外(20 - 500纳克/毫升),所有物种中约90%的药物与血浆蛋白结合;分别以50毫克/千克、5毫克/千克的剂量给大鼠和犬口服给药,以及以每人200毫克的剂量给人体口服给药后,大鼠体内的结合率为69 - 88%,犬为90 - 95%,人体为77 - 89%。

相似文献

1
Determination of plasma protein binding of propafenone in rats, dogs and humans by highly sensitive gas chromatography-mass spectrometry.用高灵敏度气相色谱-质谱法测定大鼠、犬和人体中普罗帕酮的血浆蛋白结合率。
J Chromatogr. 1985 Jun 14;341(2):305-11. doi: 10.1016/s0378-4347(00)84044-x.
2
Simultaneous determination of propafenone and 5-hydroxypropafenone in plasma by means of high pressure liquid chromatography.采用高压液相色谱法同时测定血浆中的普罗帕酮和5-羟基普罗帕酮。
Arzneimittelforschung. 1984;34(11):1455-60.
3
The metabolic fate of 2H-labelled propafenone in man.人体内2H标记普罗帕酮的代谢转归
Eur J Drug Metab Pharmacokinet. 1984 Jan-Mar;9(1):41-55. doi: 10.1007/BF03189604.
4
In-vitro plasma protein binding of propafenone and protein profile in eight mammalian species.
Res Commun Chem Pathol Pharmacol. 1989 Jun;64(3):435-40.
5
Studies on the metabolism of propafenone. 1st Comm.: synthesis and chromatographic/mass spectrometric properties of the labelled compound and of the reference substances.普罗帕酮的代谢研究。第一篇通讯:标记化合物及对照品的合成与色谱/质谱特性
Arzneimittelforschung. 1984;34(8):843-9.
6
Identification of a metabolite of propafenone in human urine by means of high-performance liquid chromatography and gas chromatography--mass spectrometry.通过高效液相色谱法和气相色谱 - 质谱联用法鉴定人尿液中普罗帕酮的一种代谢物。
J Chromatogr. 1983 Nov 11;278(1):173-8. doi: 10.1016/s0378-4347(00)84770-2.
7
Determination of propafenone in serum or plasma by electron-capture gas chromatography.采用电子捕获气相色谱法测定血清或血浆中的普罗帕酮。
J Chromatogr. 1982 Nov 12;232(2):435-9. doi: 10.1016/s0378-4347(00)84186-9.
8
[Studies on the analysis of propafenone by means of internal analogue standardization (author's transl)].
Arzneimittelforschung. 1982;32(1):1-6.
9
[Clinical pharmacology of propafenone].
G Ital Cardiol. 1984 Apr;14(4):285-92.
10
Studies on the metabolism of propafenone. 2nd comm.: studies on the biotransformation in the dog.普罗帕酮的代谢研究。第二篇通讯:犬体内生物转化的研究。
Arzneimittelforschung. 1984;34(9):972-9.

引用本文的文献

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Physiologically based pharmacokinetic tissue compartment model selection in drug development and risk assessment.生理基于药代动力学组织隔室模型在药物研发和风险评估中的选择。
J Pharm Sci. 2012 Jan;101(1):424-35. doi: 10.1002/jps.22768. Epub 2011 Oct 3.
2
Propafenone. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias.普罗帕酮。对其药理学、药代动力学及在心律失常治疗中的应用的重新评估。
Drugs. 1993 Jan;45(1):85-130. doi: 10.2165/00003495-199345010-00008.
3
Propafenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias.
普罗帕酮。对其药效学和药代动力学特性以及在心律失常治疗中的治疗用途的综述。
Drugs. 1987 Dec;34(6):617-47. doi: 10.2165/00003495-198734060-00001.
4
Canine digitalis arrhythmia as a model for detecting Na-channel blocking antiarrhythmic drugs: a comparative study using other canine arrhythmia models and the new antiarrhythmic drugs, propafenone, tocainide, and SUN 1165.犬洋地黄心律失常作为检测钠通道阻滞抗心律失常药物的模型:使用其他犬心律失常模型及新型抗心律失常药物普罗帕酮、妥卡尼和SUN 1165的比较研究
Heart Vessels. 1985 Feb;1(1):29-35. doi: 10.1007/BF02066484.
5
Tissue distribution of propafenone in the rat after intravenous administration.静脉注射后普罗帕酮在大鼠体内的组织分布。
Eur J Drug Metab Pharmacokinet. 1991 Jan-Mar;16(1):23-7. doi: 10.1007/BF03189870.