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使用磺胺脒、异喹胍和苯妥英对抑郁患者进行表型分析时马普替林和去甲基马普替林的乙酰化作用

Acetylation of maprotiline and desmethylmaprotiline in depressive patients phenotyped with sulfamidine, debrisoquine, and mephenytoin.

作者信息

Baumann P, Bosshart P, Gabris G, Gastpar M, Koeb L, Woggon B

机构信息

Clinique Psychiatrique Universitaire de Lausanne, Basle, Switzerland.

出版信息

Arzneimittelforschung. 1988 Feb;38(2):292-6.

PMID:3370079
Abstract

A gas chromatographic/mass spectrometric method (using either electron impact or chemical ionisation with methane or ammonia) is described for the quantitative analysis of maprotiline (MP, Ludiomil), N-acetylmaprotiline (AcMP) and N-acetyldesmethylmaprotiline (AcDMP) in whole blood or plasma. In two groups (A and B) of 82 and 53 depressive patients treated clinically with MP for 10 and 21 days, respectively, plasma and whole blood MP was monitored during the treatment. In group A, all subjects were phenotyped with debrisoquine and mephenytoin, and 44 with sulfamidine. 5 patients were poor metabolizers of debrisoquine and 2 of mephenytoin; 18 subjects were fast acetylators of sulfamidine. Traces of AcMP were found only in two patients. AcDMP was present in levels below 2 ng/ml in the plasma of most of the patients in group A. In group B, AcDMP levels between 2.4-14.6 ng/ml of whole blood were found in 9 patients. The mass spectral data suggest the presence of another, unknown MP metabolite interfering partly with the analysis of AcDMP. The presence of AcDMP seemed not to be related to the phenotype of the patients as determined by the pharmacogenetic tests.

摘要

本文描述了一种气相色谱/质谱法(采用电子轰击或甲烷或氨的化学电离),用于定量分析全血或血浆中的马普替林(MP,路滴美)、N - 乙酰马普替林(AcMP)和N - 去甲基乙酰马普替林(AcDMP)。在分别用MP临床治疗10天和21天的两组(A组和B组)抑郁症患者中,A组有82例,B组有53例,治疗期间监测了血浆和全血中的MP。在A组中,所有受试者都用异喹胍和美芬妥英进行了表型分析,44例用磺胺脒进行了分析。5例患者是异喹胍的慢代谢者,2例是美芬妥英的慢代谢者;18例受试者是磺胺脒的快乙酰化者。仅在两名患者中发现微量的AcMP。A组大多数患者血浆中AcDMP的水平低于2 ng/ml。在B组中,9例患者全血中AcDMP水平在2.4 - 14.6 ng/ml之间。质谱数据表明存在另一种未知的MP代谢物,部分干扰了AcDMP的分析。AcDMP的存在似乎与通过药物遗传学测试确定的患者表型无关。

相似文献

1
Acetylation of maprotiline and desmethylmaprotiline in depressive patients phenotyped with sulfamidine, debrisoquine, and mephenytoin.使用磺胺脒、异喹胍和苯妥英对抑郁患者进行表型分析时马普替林和去甲基马普替林的乙酰化作用
Arzneimittelforschung. 1988 Feb;38(2):292-6.
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Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin.阿米替林的药代动力学与临床反应:II. 通过异喹胍和甲妥英羟基化评估代谢多态性。
Int Clin Psychopharmacol. 1986 Apr;1(2):102-12. doi: 10.1097/00004850-198604000-00002.
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Debrisoquine hydroxylation and sulfamethazine acetylation in a Chinese population.
Zhongguo Yao Li Xue Bao. 1990 Sep;11(5):385-8.
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GLC-mass spectrometric determination of maprotiline and its major metabolite using stable isotope-labeled analog as internal standard.使用稳定同位素标记类似物作为内标,通过气相色谱-质谱联用技术测定马普替林及其主要代谢物
J Pharm Sci. 1980 Jun;69(6):684-7. doi: 10.1002/jps.2600690619.
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Genetic predisposition to bladder cancer: ability to hydroxylate debrisoquine and mephenytoin as risk factors.
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[Pharmacogenetics of antidepressant metabolism. Value of the debrisoquin test].
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[The concentrations of amitriptyline, maprotiline and their demethylated metabolites, nortriptyline and desmethylmaprotiline, in rat plasma and brain].[大鼠血浆和脑中阿米替林、马普替林及其去甲基代谢产物去甲替林和去甲马普替林的浓度]
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