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Drug Interaction of Herbal and Western Medicines

Drug Interaction of Herbal and Western Medicines_tabaye

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Drug Interaction of Herbal and Western Medicines

اسلاید 1: EHFG 5-8, Oct. 20051www.tabaye.ir

اسلاید 2: EHFG 5-8, Oct. 20052Drug Interaction of Herbal and Western Medicines胡幼圃 教授兼主任Prof. Oliver Yoa-Pu Hu, Ph.D.DeanResearch, Development and Continuing EducationNational Defense Medical CenterTaipei, Taiwan, R.O.C.

اسلاید 3: EHFG 5-8, Oct. 20053OutlineCurrent Status of Herbal or Traditional Medicines in Eastern and Western WorldAdverse Events and Drug-Interaction Caused by Herbal or Traditional MedicinesEvidences Based Drug-Interaction Caused by Herbal or Traditional MedicinesConclusions and Suggestions

اسلاید 4: EHFG 5-8, Oct. 20054 Current Status of Herbal or Traditional Medicines in Eastern and Western World

اسلاید 5: EHFG 5-8, Oct. 20055Insurance Paid for Herbal MedicinesGerman health insurance paid $283 million in reimbursements for prescribed ginkgo, St. John’s wort, mistletoe, saw palmetto, ivy, hawthorn, stinging nettle root, myrtol, phytosterols, and cucurbita in 2003. French health insurance paid $91 million in partial reimbursements for ginkgo, saw palmetto, and pygeum prescriptions with a total value of $196 million in 2002.NEJM 352:12, 2005

اسلاید 6: EHFG 5-8, Oct. 20056European Market for Over-The-Counter Herbal Medicines in 2003NEJM 352:12, 2005*Taiwan Herbal Medicines market was 4.0 billion in 2002Distribution of the $4.96 Billion European Market for Over-the-CounterHerbal Medicines in 2003.

اسلاید 7: EHFG 5-8, Oct. 20057Herbal Medicines in USIn a 1990 survey of 1,539 adults, 33.8% of respondents used herbal medicines or nutritional supplements. By 1997, the number had increased to 42.1%, with most people paying the cost out-of-pocket.Approximately 40% of patients who use alternative therapies do not disclose this information to their doctor.AM J Ophthalmol 138:639, 2004

اسلاید 8: EHFG 5-8, Oct. 20058Adverse Events and Drug-Interaction Caused by Herbal or Traditional Medicines

اسلاید 9: EHFG 5-8, Oct. 20059Effect of Various CYP Isoforms by Herbal Constituents (I)Drug Metabolism Reviews 35:35, 2003(from Zizyphi fructus)CME = Crude methanolic extract; DAD = Diallyl disulfide; DAS = Diallyl sulfide; H = Human; M = Mouse; PH = PrimaryHepatocytes; PXR = Pregnane X receptor; R = Rat; SJW = St. John’s wort.

اسلاید 10: EHFG 5-8, Oct. 200510Effect of Various CYP Isoforms by Herbal Constituents (II)Drug Metabolism Reviews 35:35, 2003CME = Crude methanolic extract; DAD = Diallyl disulfide; DAS = Diallyl sulfide; H = Human; M = Mouse; PH = PrimaryHepatocytes; PXR = Pregnane X receptor; R = Rat; SJW = St. John’s wort.

اسلاید 11: EHFG 5-8, Oct. 200511Effect of Various CYP Isoforms by Herbal Constituents (III)Drug Metabolism Reviews 35:35, 2003CME = Crude methanolic extract; DAD = Diallyl disulfide; DAS = Diallyl sulfide; H = Human; M = Mouse; PH = PrimaryHepatocytes; PXR = Pregnane X receptor; R = Rat; SJW = St. John’s wort.

اسلاید 12: EHFG 5-8, Oct. 200512Known Pharmacokinetic Herb-Drug Interactions (I)Drug Metabolism Reviews 35:35, 2003

اسلاید 13: EHFG 5-8, Oct. 200513Known Pharmacokinetic Herb-Drug Interactions (II)Drug Metabolism Reviews 35:35, 2003

اسلاید 14: EHFG 5-8, Oct. 200514Potential Interactions between Herbs and Conventional Drugs (I)NEJM 347:2046, 2002

اسلاید 15: EHFG 5-8, Oct. 200515Potential Interactions between Herbs and Conventional Drugs (II)NEJM 347:2046, 2002

اسلاید 16: EHFG 5-8, Oct. 200516Potential Interactions between Herbs and Conventional Drugs (III)NEJM 347:2046, 2002

اسلاید 17: EHFG 5-8, Oct. 200517Evidence Based Drug-Interaction Caused by Herbal or Traditional Medicines and Food

اسلاید 18: EHFG 5-8, Oct. 200518SimvastatinHMG-CoA reductase inhibitorAs a substrate for both CYP3A4 and P-gpBioavailability < 5%

اسلاید 19: EHFG 5-8, Oct. 200519In Vitro Inhibiting CYP3A4 in Liver Microsomes with Herbal and Food Constituents (PC: ketoconazole)

اسلاید 20: EHFG 5-8, Oct. 200520Effect of HUCHE015 on Total Simvastatin Absorption on Female SD Rats by Oral*12.3 g of green-tea leaf contain 20 mg of HUCHE015

اسلاید 21: EHFG 5-8, Oct. 200521PK Parameters of Simvastatic Acid of Female SD Rats after Oral Simvastatin Simvastatin 50 mg/kg in DMSO and HUCHE015 20 mg/kg in DMSO*12.3 g of green-tea leaf contain 20 mg of HUCHE015

اسلاید 22: EHFG 5-8, Oct. 200522FluvastatinHMG-CoA reductase inhibitorSpecifically and extensively metabolized by CYP2C9Oral bioavailability: 20-30%

اسلاید 23: EHFG 5-8, Oct. 200523Fluvastatin in SD Rats after Orally Administered Fluvastatin with or without Herbal Constituents*The herbal constituents is HUCHE070 that is very rich in Eupatorium odoratum. The dose is 9.3 mg/kg

اسلاید 24: EHFG 5-8, Oct. 200524Fluvastatin PK Parameters in SD Rats after Orally Administered Fluvastatin with or without Herbal Constituents

اسلاید 25: EHFG 5-8, Oct. 200525NalbuphineNarcotic analgesicsk-agonist, m-antagonistAdvantage: low tolerance、 addiction、 and respiratory depressionDrawback: short durationMainly Metabolized by UGT2B7Oral bioavailability less than 5%

اسلاید 26: EHFG 5-8, Oct. 200526Nalbuphine in SD Rats after Oral Nalbuphine with or without Herbal Constituents*The HUCHE035 is very rich in Artemisia capillaris and the dose is 4.5 mg/kg.

اسلاید 27: EHFG 5-8, Oct. 200527PK Parameters for SD Rats after Oral Nalbuphine with or without Herbal Constituents

اسلاید 28: EHFG 5-8, Oct. 200528Conclusions and Suggestions (I)Evidences from in vitro and in vivo studies has indicated that the constituents of herbal preparation, even food, interact with various drug metabolic enzymes extensively.High throughput screening assays combine with in vivo or clinical study will be a useful strategy to examine the herb-drug interactions

اسلاید 29: EHFG 5-8, Oct. 200529Conclusions and Suggestions (II)Medical and pharmaceutical communities had been slow to respond to this important issueGovernment, industry and medical societies should vigorously examine the possible drug interaction with the most commonly used herbal drugsDrug Insert should clearly indicate the clinically significant drug interaction with commonly used herbs, dietary supplements, healthy food and traditional medicines

اسلاید 30: EHFG 5-8, Oct. 200530Thanks for your attention

اسلاید 31: EHFG 5-8, Oct. 200531Problems Caused from Herbal MedicinesPotential adulterants and contaminations that can affect the quality of herbal remediesPlants containing belladonna or pyrrolizidine alkaloids, microorganisms, aflatoxins, bacterial endotoxin, pesticides, fumigation agents, toxic metals and DrugsPotential adverse effects of herbal remedies and their major constituentsCardiotoxicity: aconire root ruberHepatoxicity: certain herbs rich in anthranoids and protoberberine alkaloids, green-tea leafNeurotoxicity or convulsions: Kava rhizomeRenal toxicity: -Aescin (saponin mixture from horse-chestnut seed)NEJM 347:2046, 2002

اسلاید 32: EHFG 5-8, Oct. 200532

اسلاید 33: EHFG 5-8, Oct. 200533Potential Adulterants and Contaminants that Can Affect the Quality of Herbal RemediesNEJM 347:2046, 2002

اسلاید 34: EHFG 5-8, Oct. 200534Potential Adverse Effects of Herbal Remedies and Their Major ConstituentsNEJM 347:2046, 2002

اسلاید 35: EHFG 5-8, Oct. 200535Effects of St. John’s Wort Constituents on the Activity of Various CYPsDrug Metabolism Reviews 35:35, 2003

اسلاید 36: EHFG 5-8, Oct. 200536Induction of Various CYP Isoforms by Herbal Constituents (I)Drug Metabolism Reviews 35:35, 2003

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