Disposition of Heptabarbitone in the Rat: Identification of a New Metabolite by Tandem Mass Spectrometry

Author:

Stijnen A M1,Heeremans C E M2,Van Bezooijen C F A3,Niessen W M A2,Danhof M1

Affiliation:

1. Center for Bio-Pharmaceutical Sciences, Division of Pharmacology, University of Leiden, PO Box 9503, 2300 RA Leiden, The Netherlands

2. Center for Bio-Pharmaceutical Sciences, Division of Analytical Chemistry, University of Leiden, PO Box 9502, 2300 RA Leiden, The Netherlands

3. TNO institute for Ageing and Vascular Research, PO Box 2215, 2301 CE, Leiden, The Netherlands

Abstract

Abstract The purpose of this study was to elucidate the structure of a metabolite of heptabarbitone, the occurrence of which was reported previously in a number of pharmacokinetic and pharmacodynamic modelling studies. By application of thermospray liquid chromatography (tandem) mass spectrometry, the identity of the metabolite was proposed to be 5-ethyl-5-(1′,[3′ or 6′]-cycloheptadienyl)-barbituric acid. By measuring the ratios between the areas under the concentration time curves of the metabolite and heptabarbitone after administration of three different intravenous dosages of heptabarbitone, it was shown that the exposure to the metabolite is directly correlated with the exposure of heptabarbitone.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference14 articles.

1. Metabolic fate of hexobarbital;Bush;Drug Metab. Rev.,1972

2. Kinetics of drug action in disease states. I. Effect of infusing rate on phenobarbital concentrations in serum, brain and cerebrospinal fluid of normal rats at onset of loss of righting reflex;Danhof;J. Pharmacol. Exp. Ther.,1984

3. Kinetics of drug action in disease states. V. Acute effect of urea infusion of phenobarbital concentrations in rats at onset of loss of righting reflex;Danhof;J. Pharmacol. Exp. Ther.,1985

4. Strategy to assess the role of (inter)active metabolites in pharmacodynamic studies in vivo: a model study with heptabarbital;Dingemanse;J. Pharm. Pharmacol.,1988

5. Application of serial sampling of cerebrospinal fluid in pharmacodynamic studies with a drug active in the CNS: heptabarbital concentrations at onset and offset of loss of righting reflex in rats;Dingemanse;Neuropharmacology,1988

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3