TCM Pharmacology

New England School of Acupuncture Clinical Pharmacology Yin Xing; Ginkgo Biloba The Interactions with Drugs By Pai Jung Huang June 1st 2006 1. Name: • Pinyin: Yin Xing; Bai Guo; • Pharmaceutical: Semen Ginkgo • Botanical : Ginkgo Biloba (Yin Xing) • Properties: sweet, bitter, astringent, neutral • Channel: Lung • Safety Index: Slightly toxic 2. Mechanism of action: • Arrests Wheezing and Dispels Phlegm • Restrain the Leakage of Fluids from the Lower Jiao 3. Name(s) of the drug which interact with Yin Xing -- Drug names based on CYP3A Substrates 1. Amitriptyline (Elavil) 2. Benzodiazepines o Alprazolam ( Xanax ) o Triazolam ( Halcion ) o Middazolam ( Versed ) 3. Calcium blocker 4. Carbamazepine ( Tegretol ) 5. Cisapride ( Propulsid ) 6. Dexamethasone ( Decardron ) 7. Erythromycin 8. Ethinyl estradiol (Estraderm, Estrace ) 9. Glyburide (Glynase, Micronase ) 10. Imipramine (Tofranil ) 11. Ketoconazole ( Nizoral ) 12. Lovasztatin ( Mevacor ) 13. Nerfazodone (Serzone ) 14. Terfenadine ( Seldane ) 15. Astemizole ( Calan, Isoptin) 16. Sertraline ( Zoloft ) 17. Testosterone 18. Theophylline* 19. Venlafaxine ( Effexor )

20. Protease inhibitor o Ritonavir ( Norvir ) o Saquinavir ( Invirase ) o Indinavir ( Crixivan ) o Nelfinavir ( Viracept ) -- Drig names based on CYP2C19 Substrates 1. Clomipramine ( Anafranil ) 2. Diazepam ( Valium )* 3. Imipramine ( Tofranil )* 4. Omeprazole ( Prilosec ) 5. Propranolol ( Inderal )* -- Drug names based on CYP2C9 substrates 1. Nonsteroidal anti-inflammatory drugs 2. Phenytoin ( Dilantin ) 3. S-warfarin 4. Torsemide (Demadex ) * means also involving other isoform enzyme 4. Mechanism of possible interaction: By Jason Barker, ND and Chris Meletis, ND’s article: Ginkgo was shown to inhibit CYP2C9, CYP2C19 and CYP3A4 in human studies. From the study of Dr. Steve H Yale and Dr. Ingrid Glurich: Moderate inhibition of CYP2C9 was seen with G. biloba; G. biloba also showed mild-to-moderate inhibition of CYP3A4 depending on the model substrate. 5. NESA comments: Drug metabolism in the body is to make drugs more water soluble and thus more readily excreted in the urine or bile. One common way of metabolizing drugs involves the alteration of functional groups on the parent molecule (e.g., oxidation) via the cytochrome P450 enzymes. These enzymes are most predominant in the liver but can also be found in the intestines, lungs and other organs. These cytochrome P450 enzymes are designated by the letters "CYP" followed by an Arabic numeral, a letter and another Arabic numeral (e.g., CYP2D6). Each enzyme is termed an isoform since each derives from a different gene. Herb-Drug interactions involving the cytochrome P450 isoforms generally result from one of two processes, enzyme inhibition or enzyme induction. Enzyme inhibition usually involves competition with another drug for the enzyme binding site. Many herb-drug interactions are a result of inhibition or induction of cytochrome P450 enzymes (CYP450). The report will discuss the Yin Xing cause a result of inhibition of cytochrome P450: CYP3A, CYP2C19 and CYP2C9.

The CYP3A subfamily is involved in many clinically significant drug interactions, including those involving nonsedating antihistamines and cisapride (Clarytin), that may result in cardiac dysrhythmias, and the CYP3A4 enzymes is involved in drug interactions involving theophylline. Since Yin Xing is an inhibitor of CYP3A4, so we have to be very careful to use the substrates drugs of CYP3A4, and to avoid the side effect of its slow metabolism rate affected by Yin Xing. CYP2C19 is completely absent in 3 percent of Caucasians and 20 percent of Japanese. Drugs metabolized by this isoform include omeprazole (Prilosec), lansoprazole (Prevacid) and diazepam (Valium). However, clinical examples of excessive or adverse drug effects in people who are CYP2C19-deficient are lacking. It seems we do not have to worry too much. But eventually, when patient take Yin Xing with Prilosec, Prevacid (proton pump inhibitors for peptic ulcer disease) or Valium ( common sedative ), we have to monitor the side effect closely as well. Most metabolism of S-warfarin is by means of CYP2C9, and inhibition of this isoform results in several clinically important drug interactions. More famous drug is Phenytoin. Phenytoin is primarily metabolized via CYP2C9. Yin Xing is a moderate inhibitor of CYP2C9. Although it is less likely to cause clinically significant inhibition of phenytoin and S-warfarin metabolism at suggested Yin Xing dosages, we still have to pay more attentions if patients take S-warfarin or Phenytoin combing with Yin Xing. By understanding the unique functions and characteristics of these enzymes, practitioners may better anticipate and manage herb - drug interactions and may predict or explain an individual's response to a particular therapeutic regimen. 6. Major reference: (1) Barkert, Jason; Meletis, Chris. Popular Botanical Medicines and Cancer Drug Interactions: A Review. Townsend Letter for Doctors & Patients, Jul2005 Issue 264, p110-112. (2) Yale, Steven H.; Glurich, Ingrid. Analysis of the Inhibitory Potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the Metabolic Activity of Cytochrome P450 3A4, 2D6, and 2C9. Journal of Alternative & Complementary Medicine, Jun2005, Vol. 11 Issue 3, p433-439. (3) Sorensen J Maria. Herb–Drug, Food–Drug, Nutrient-Drug, and Drug–Drug Interactions: Mechanisms Involved and Their Medical Implications. Journal of Alternative & Complementary Medicine, Vol. 8 Issue 3, 2002, p293-308. 7. Full text paper Yale, Steven H.; Glurich, Ingrid. Analysis of the Inhibitory Potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the Metabolic Activity of Cytochrome P450 3A4, 2D6, and 2C9. Journal of Alternative & Complementary Medicine, Jun2005, Vol. 11 Issue 3, p433-439.