1、rmit university10th scicc, guangzhou, china, 2008 recent progress in the evidence-based application of herbal medicines for cardiovascular diseases professor shufeng zhou, md, phdschool of health scienceswho collaborating center for traditional medicinermit university, bundoora, victoria 3083austral

2、iaphone: tel: +61 3 9925 7794; fax: +61 3 9925 7178email: .au11 april 2008rmit university10th scicc, guangzhou, china, 2008 an overview of global herbal use all folk medicine includes the use of plant products. 11,145 species of herbal plants worldwide; 534 species of plants for

3、chinese medicine. who definition botanical origin, without adulteration of any synthetic drugs. legal status: food supplements (fda & tga) “dshea”; drugs/health foods (sfda of china). us$25 billion; market value 1015%/per year. 2 billion in australia. 40% caucasian and 80% asians use or used her

4、bs.rmit university10th scicc, guangzhou, china, 2008 active componentsbiotransformation excretionabsorptionresponse/toxicity?rmit university10th scicc, guangzhou, china, 2008 preclinical stagephase iphase iiphase iiiphase ivclinical trials of herbal medicinesgeneral acceptance of humanssafety and ef

5、ficacymore data on safety and efficacyrmit university10th scicc, guangzhou, china, 2008 challenges for herbal clinical trials dosage & formulation: standardized or individualized? biomarkers? safety profiles? pharmacokinetics data?rmit university10th scicc, guangzhou, china, 2008 herbspkpdrmit u

6、niversity10th scicc, guangzhou, china, 2008 pharmacokinetics of tpns formula in stroked patientsrmit university10th scicc, guangzhou, china, 2008 omega1，12，23，34，4residual variability (sigma；cv% if proportional, s.d. if additive)1，12，2final estimate0.1320.03180.00010.3630.007521.00e-005rse (%)30.246

7、.5.47.539.6.95% confidence intervallbound0.0540.00279.0.02490.00168.ubound0.2100.0608.0.7030.0134.cv (%)36.317.81.0060.38.67sd=0.00316rmit university10th scicc, guangzhou, china, 2008 dosage (mg/kg) ptttfibapttrmit university10th scicc, guangzhou, china, 2008 injection rate (mg/min) ptttfibapttrmit

8、university10th scicc, guangzhou, china, 2008 integrated conc. (g/ml) ptptttfibapttrmit university10th scicc, guangzhou, china, 2008 rmit university10th scicc, guangzhou, china, 2008 herbal medicines as multi-component therapeutics it is possible to integrate pk and pd for herbal medicines. challenge

9、s: multi-component therapeutics? which marker compounds to measure? how to determine therapeutic window?rmit university10th scicc, guangzhou, china, 2008 herb-drug interactions: underestimated patients: 70% do not reveal their herbal use to their doctors/pharmacists in western countries legal issue:

10、 rigorous preclinical and clinical assessments not required difficulties in the studies; poor clinical studies lack of adr reporting systemrmit university10th scicc, guangzhou, china, 2008 types of clinical reports on herb-drug interactionsn = 85rmit university10th scicc, guangzhou, china, 2008 what

11、 herbs interact with drugs?n = 85rmit university10th scicc, guangzhou, china, 2008 what drugs interact with herbs?n = 85drug properties: narrow therapeutic index; extensive metabolism; substrates of cyps and/or pgp.rmit university10th scicc, guangzhou, china, 2008 herbinteracting drugsdangguiwarfari

12、ndanshen warfaringarlic saquinavir, ritonavir, warfarin, chlorpropamide ginkgo trazodone, warfarin, digoxinginsengalcohol, phenelzine, warfarin hawthorndigoxin (no change)kavaalcohol, alprazolam, bromazepam, l-dopamilk thistleindinavirpiperinepropranolol, rifampin, sparteine, theophylline, phenytoin

13、rmit university10th scicc, guangzhou, china, 2008 toxicity due to herb-drug interactionsherb + drugtoxicitysjw + cyclosporine aorgan rejectionsjw + oral contraceptivesbreakthrough bleeding & unplanned pregnanciesgarlic + chlorpropamidehypoglycemiakava + alprazolamsemicomakava + l-dopa“off” perio

14、ds in parkinson diseaseginseng + phenelzinemaniaginkgo + trazodonecomaginkgo + warfarin/aspirin bleedingdanshen + warfarinbleedingrmit university10th scicc, guangzhou, china, 2008 sjw-drug interactions antidepressants: amitriptyline; ssris (sertraline zoloft) anticancer drug: irinotecan (cpt-11) ant

15、icoagulants: warfarin (coumadin), phenprocoumon antihistamine: fexofenadine anti-hiv agents: pi: indinavir; rti: nevirapine bronchodilator: theophylline hypoglycemics: tolbutamide cardiovascualr drugs: digoxin, simvastatin opiates: methadone, loperamide oral contraceptives sedatives: alprazolam &

16、; midazolam immunosuppressants: cyclosporine & tacrolimusrmit university10th scicc, guangzhou, china, 2008 051015202530010203040506070before treatment of st. johns wortafter treatment of st. johns wort(a)time (h)conc. of nif (ng/ml)05101520253001020304050(b)befor treatment of st. johns wortafter

17、 treatment of st. johns worttime (h)conc. of dnif (ng/ml)rmit university10th scicc, guangzhou, china, 2008 mechanisms for herb-drug interactionsdrug responsemetabolizing enzymes(cyps) identical targetstransporters(pgp)different targetspharmacokinetics (pk)pharmacodynamics (pd)rmit university10th sci

18、cc, guangzhou, china, 2008 herb-cyp interactionsherbcyps affectedsjwmost cyp (mainly cyp3a4)garliccyp2c, 2d, 2e, 3apiperinecyp1a, 2c, 3alicorice cyp1a, 2a, 2c, 3akavacyp1a, 2c, 2d, 3a ginseng cyp3a4, 2d, 2cginkgo cyp2b, 3abaizhicyp1a, 2d, 2e, 3adangguicyp1a, 3armit university10th scicc, guangzhou, c

19、hina, 2008 herb-pgp interactionsherbmodulation of pgpcurcumininhibitionhawthorn?garlicinhibitionginsengmostly inhibitiongreen teainhibitionmilk thistleinhibitionpiperineinhibition sjwinductionrosemaryinhibitionrmit university10th scicc, guangzhou, china, 2008 ooohohyperforinohoohoohohohohhypericinoo

20、hoohohohohoohohohohooohohoohohohohoohohooohohquercetinchlorogenic acidi3,ii8-biapigeninrmit university10th scicc, guangzhou, china, 2008 rmit university10th scicc, guangzhou, china, 2008 herbal labeling what: identity, quantity of contents, identified active ingredient by common name or proprietary

21、blend. how to use: route, dose daily, etc who: name and place of manufacturer, packer or distributor. what to claim “this statement has not been evaluated by the food and drug administration”. “this product is not intended to diagnose, treat, cure, or prevent any diseases”. - “it is not advisable to use in combination with”rmit university10th scicc, guangzhou, china, 2008 acknowledgmentsprof. guangji wangprof. xiyo