青蒿素及其活性衍生物在生物样品中的测定及代谢动力学研究  

DETERMINATION OF QINGHAOSU AND ITS ACTIVE DERIVATIVES IN BIOLOGICAL FLUIDS AND STUDIES ON THE PHARMACOKINETICS OF THESE COMPOUNDS

作　　者：宋振玉[1] 赵凯存[1] 

机构地区：[1]中国医学科学院药物研究所

出　　处：《中国临床药理学杂志》1989年第1期12-17,11,共7页The Chinese Journal of Clinical Pharmacology

摘　　要：青蒿素是从我国药草黄花蒿中分离出的一种抗疟有效成分,因其结构特殊,疗效高,毒性小,且对抗氯喹疟原虫感染也有效,受到国内外重视。为使青蒿素及其活性衍生物成为符合国际标准的新药,很多单位对这些化合物在生物样本内的含量测定方法和药代动力学进行了研究,本文对这些研究所取得的结果作了简单复习和评述。Qinghaosu (QHS), a1so known as artemisinine and arteannuin, is a sesquiterpene peroxide isolated from the Chinese herb Artemisiaannua L. Pharmacological and clinical studies showed that it is highlyactive against falciparum and vivax malaria infections even in chloroquineresistant cases and appears to have a mode of action different from otherexisting antimalarials. Since its discovery in 1972 by Chinese scientists,more than one hundred derivatives have been synthesized among them arte-sunate, aute mether and dihydroqinghaosu were found to be more active thanQHS itself.For studies of pharmacokinetics of these drugs in higher animals including human beings,development of a sensitive method of determination in body fluids with high specificity is a prerequisite,Early studies on the disposition of QHS were carried out using either C-or H-labeled compound or a TLC-densitometric method which lack sensitivity and specificity.Several methods of chormogenic chemical derivatization of QHS for TLC and HPLC determination have been described but no detailed report of clinical pharmacokinetic studies using these methods has been forund in the literature.A reductive HPLC-EC method using a Model 301 polarographic detector for the simultaneous detrmination of artesunate and its active derivative (metabolite) dihydroqinghaosu in human plasma had been eatablished wi8ch is sensitive enough to enable the authors to study the pharmackinetics of artesunate in four volunters given an i.v.doese of 3.3-4.4mg/kg.However,this method in cunbersome and needs an extracion procedure,A redinoimmunoassay method has been established which is precise,simple sensitve dihydroqinghaogu,Auti-QHS antibody was obtained by immunizing sheep with conjuate.Studjes on the harmacone tice of these compounds in animals and human volunteers using these methods are briefly reviewed.

关 键 词：青蒿素 衍生物 抗疟药 药代动力学 

分 类 号：R978.62[医药卫生—药品]