Interaction Potential of Glycyrrhiza uralensis,a Traditional

PHYTOTHERAPY RESEARCHPhytother. Res. 23, 603–607 (2009)

Published online 27 January 2009 in Wiley InterScienceDRUG–DRUG INTERACTION OF GLYCYRRHIZA URALENSIS(http://doc.guandang.net) DOI: 10.1002/ptr.2450

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Study on the Pharmacokinetics Drug–DrugInteraction Potential of Glycyrrhiza uralensis,a Traditional Chinese Medicine, with Lidocainein Rats

Jingcheng Tang1, Xiaohong Song1, Min Zhu2 and Jinnan Zhang1*

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School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, ChinaDepartment of Pharmacy, Chinese University of HK, Hong Kong

Drug–drug interaction potentials of an herbal medicine named Glycyrrhiza uralensis was investigated in ratsvia in vitro and in vivo pharmacokinetic studies. P450 levels and the metabolic rate of lidocaine in the livermicrosomes prepared from different treatment groups were measured. In a separate in vivo pharmacokineticstudy, the pharmacokinetic parameters of lidocaine in plasma and urine were estimated. P450 levels in the ratspretreated by Glycyrrhiza uralensis were signi cant higher than that in the non-treatment control. The in-crease in P450 levels was dose-dependent. Glycyrrhiza uralensis (1 and 3g/kg) increased P450 levels by 62% and91%, respectively, compared with the non-treatment control (0.695nmol/mg protein). The metabolic rate oflidocaine in the liver microsomes was signi cantly higher in the herb pretreated rats. The pharmacokineticpro le of lidocaine was signi cantly modi ed in the rats with the herbal pretreatment. Elimination half-liveswere shortened by 39%, and total clearances were increased by 59% with the pretreatment of Glycyrrhizauralensis. In conclusion, Glycyrrhiza uralensis showed induction effect on P450 isozymes. Ef cacy and safetypro les of a drug may be affected when the herbal products or herbal prescriptions containing the plantmedicine were concomitantly used. Copyright © 2009 John Wiley & Sons, Ltd.

Keywords: herb–drug interaction; herbal medicine; Glycyrrhiza uralensis; hepatic enzyme induction; P450 isozymes; lidocaine.

INTRODUCTION

In the Oriental countries, the use of herbal medicinecombined with conventional medicines is common,especially for the treatment of chronic diseases, such ascancers, immunological disorders, chronic in ammationsand various infections. In Western countries, the herbalmedicine is being used increasingly by the generalpublic on a self-selection basis to either replace or com-plement conventional medicines (Newall et al., 2002).Therefore, there is an increasing concern for herb–druginteractions when they are concomitantly administered.Although some herb–drug interaction studies have beenconducted on limited herbal products, such as ginsengand St Johns Wort (Fugh-Berman, 2000; Zhu et al.,1999), the studies are far from extensive as a muchbroader range of herb has been used in medicalpractice either as a single agent or, in most cases, ascombinations composed of 5–20 different kinds of herbs.Apparently, it is dif cult to study all herbs or herbalcombinations with frequently used Western medicines.However, it is possible to single out several commonlyused herbal medicines that may have herb–drug inter-* Correspondence to: Jinnan Zhang, School of Chemical Biology andPharmaceutical Sciences, Capital Medical University, Beijing 100069, P.R.China.

E-mail: jnzhang_cums@http://doc.guandang.net

Contract/grant sponsor: National Nature Science Foundation of China;contract/grant number: 20571012 and 20871019.Copyright © 2009 John Wiley & Sons, Ltd.action potentials and to explore the underlying mecha-nisms. Glycyrrhiza uralensis is one of most frequentlyused Chinese medicines presenting in >90% of herbalprescriptions. So in this study, Glycyrrhiza uralensis isdiscussed for testing its potential on hepatic enzymeinductions.

Lidocaine is a widely used local anesthetic and anti-arrhythmic drug. Some literatures suggest that lidocainewas primarily metabolized in the liver to monoethylgly-cine xylidide (MEGX) and glycine xylidide (GX) bythe cytochrome P-450 3A4-dependent mono-oxygenasesystem (Jadwiga et al., 2004; Orszulak-Michalak et al.,2002). Therefore, both in vitro and in vivo pharmaco-kinetic studies of lidocaine were conducted in ratspretreated or not pretreated with the herb.

MATERIALS AND METHODS

Chemicals, herbal materials and animals. Lidocaine,phenacetin, NADPH, glucose-6-phosphate (G-6-P) andglucose-6-phosphate dehydrogenase (G6P-DH) werepurchased from Sigma Chemical Co. (MO, USA).Methanol and acetonitrile (HPLC grade) were purchasedfrom Mallinckrodt-Baker Inc. (KY, USA).

Dry rhizomes of Glycyrrhiza uralensis were purchasedfrom a Tong-Ren-Tang herbal shop in Beijing. The plantspecies was identi ed as Glycyrrhiza uralensis Ficschby Professor Peng Yong, from the Institute of Medi-cinal Plants, Chinese Academy of Medical Sciences.

Received 25 June 2007Phytother. Res. 23, 603–607 (2009)

604J. TANG ET AL.

Male Sprague-Dawley rats (210–230g) were obtainedfrom the Department of Laboratory Animal Science,Capital Medical University. The animals were fastedfor 12h prior to drug administration but maintainedfree access to water. These experiments were conductedin line with the principles in Regulation on Experi-mental Animals issued by Ministry of Public Healthof China.

Preparation of herbal decoctions. The aqueous decoc-tion of Glycyrrhiza uralensis was prepared mimickingthe traditional approach, brie y, the dry rhizomes werepowdered, and 200g of the powder was added to1000mL of distilled water and immersed for 20min atroom temperature. The mixture was heated at re uxfor 30min. After ltration, the residue was extractedagain in the same way. The two extract solutions werecombined and evaporated to dryness under reducedpressure. The extraction yield was approximately 31.49±dried residues were reconstituted with distill …… 此处隐藏：18754字，全部文档内容请下载后查看。喜欢就下载吧 ……