Planta Med 2011; 77(4): 311-321
DOI: 10.1055/s-0030-1250457
Reviews
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Herbal Supplements on Drug Glucuronidation. Review of Clinical, Animal, and In Vitro Studies

Mohamed-Eslam F. Mohamed1 , Reginald F. Frye1
  • 1Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA
Further Information

Publication History

received June 29, 2010 revised Sept. 7, 2010

accepted Sept. 29, 2010

Publication Date:
03 November 2010 (online)

Abstract

The use of herbal supplements has increased steadily over the last decade. Recent surveys show that many people who take herbal supplements also take prescription and nonprescription drugs, increasing the risk for potential herb-drug interactions. While cytochrome P450-mediated herb-drug interactions have been extensively characterized, the effects of herbal extracts and constituents on UDP-glucuronosyl transferase (UGT) enzymes have not been adequately studied. Thus, the purpose of this review is to evaluate current evidence on the glucuronidation of phytochemicals and the potential for UGT-mediated herb-drug interactions with the top-selling herbal supplements in the United States and Europe. In vitro and animal studies indicate that cranberry, Ginkgo biloba, grape seed, green tea, hawthorn, milk thistle, noni, soy, St. John's wort, and valerian are rich in phytochemicals that can modulate UGT enzymes. However, the in vivo consequences of these interactions are not well understood. Only three clinical studies have investigated the effects of herbal supplements on drugs cleared primarily through UGT enzymes. Evidence on the potential for commonly used herbal supplements to modulate UGT-mediated drug metabolism is summarized. Moreover, the need for further research to determine the clinical consequences of the described interactions is highlighted.

References

  • 1 De Smet P A. Herbal medicine in Europe–relaxing regulatory standards.  N Engl J Med. 2005;  352 1176-1178
  • 2 NBJ .NBJ's Supplement Business Report 2007. Boulder, CO; New Hope Natural Media, Penton Media Inc. 2007: 42-236
  • 3 Blumenthal M. The Complete German Commission E monographs: therapeutic guide to herbal medicines. Austin; American Botanical Council 1999
  • 4 Shorofi S A, Arbon P. Complementary and alternative medicine (CAM) among hospitalised patients: an Australian study.  Complement Ther Clin Pract. 2010;  16 86-91
  • 5 Vaabengaard P, Clausen L M. [Surgery patients' intake of herbal preparations and dietary supplements].  Ugeskr Laeger. 2003;  165 3320-3323
  • 6 Eisenberg D M, Davis R B, Ettner S L, Appel S, Wilkey S, Van Rompay M, Kessler R C. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey.  JAMA. 1998;  280 1569-1575
  • 7 Bardia A, Nisly N L, Zimmerman M B, Gryzlak B M, Wallace R B. Use of herbs among adults based on evidence-based indications: findings from the National Health Interview Survey.  Mayo Clin Proc. 2007;  82 561-566
  • 8 White C P, Hirsch G, Patel S, Adams F, Peltekian K M. Complementary and alternative medicine use by patients chronically infected with hepatitis C virus.  Can J Gastroenterol. 2007;  21 589-595
  • 9 Miller M F, Bellizzi K M, Sufian M, Ambs A H, Goldstein M S, Ballard-Barbash R. Dietary supplement use in individuals living with cancer and other chronic conditions: a population-based study.  J Am Diet Assoc. 2008;  108 483-494
  • 10 Gardiner P, Phillips R, Shaughnessy A F. Herbal and dietary supplement–drug interactions in patients with chronic illnesses.  Am Fam Physician. 2008;  77 73-78
  • 11 Gurley B J. Clinical pharmacology and dietary supplements: an evolving relationship.  Clin Pharmacol Ther. 2010;  87 235-238
  • 12 Morris C A, Avorn J. Internet marketing of herbal products.  JAMA. 2003;  290 1505-1509
  • 13 Ruschitzka F, Meier P J, Turina M, Luscher T F, Noll G. Acute heart transplant rejection due to Saint John's wort.  Lancet. 2000;  355 548-549
  • 14 Shord S S, Shah K, Lukose A. Drug-botanical interactions: a review of the laboratory, animal, and human data for 8 common botanicals.  Integr Cancer Ther. 2009;  8 208-227
  • 15 Tsourounis C, Bent S. Why change is needed in research examining dietary supplements.  Clin Pharmacol Ther. 2010;  87 147-149
  • 16 Crettol S, Petrovic N, Murray M. Pharmacogenetics of phase I and phase II drug metabolism.  Curr Pharm Des. 2010;  16 204-219
  • 17 Parkinson A. Biotransformation of Xenobiotics. Klaassen CS Casarett & Doull's Toxicology The Basic Science of Poisons. Columbus; McGraw-Hill 2001: 133-224
  • 18 Zhou S F, Xue C C, Yu X Q, Wang G. Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update.  Curr Drug Metab. 2007;  8 526-553
  • 19 Nowack R, Andrassy J, Fischereder M, Unger M. Effects of dietary factors on drug transport and metabolism: the impact on dosage guidelines in transplant patients.  Clin Pharmacol Ther. 2009;  85 439-443
  • 20 Izzo A A, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review.  Drugs. 2009;  69 1777-1798
  • 21 Skalli S, Zaid A, Soulaymani R. Drug interactions with herbal medicines.  Ther Drug Monit. 2007;  29 679-686
  • 22 Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba.  J Anal Toxicol. 2005;  29 755-758
  • 23 Whitten D L, Myers S P, Hawrelak J A, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials.  Br J Clin Pharmacol. 2006;  62 512-526
  • 24 Dutton G J. Glucuronidation of drugs and other compounds. Boca Raton, FL; CRC Press 1980
  • 25 Owens I S, Basu N K, Banerjee R. UDP-glucuronosyltransferases: gene structures of UGT1 and UGT2 families.  Methods Enzymol. 2005;  400 1-22
  • 26 Guillemette C, Levesque E, Harvey M, Bellemare J, Menard V. UGT genomic diversity: beyond gene duplication.  Drug Metab Rev. 2010;  42 22-42
  • 27 Ohno S, Nakajin S. Determination of mRNA expression of human UDP-glucuronosyltransferases and application for localization in various human tissues by real-time reverse transcriptase-polymerase chain reaction.  Drug Metab Dispos. 2009;  37 32-40
  • 28 Izukawa T, Nakajima M, Fujiwara R, Yamanaka H, Fukami T, Takamiya M, Aoki Y, Ikushiro S, Sakaki T, Yokoi T. Quantitative analysis of UDP-glucuronosyltransferase (UGT) 1A and UGT2B expression levels in human livers.  Drug Metab Dispos. 2009;  37 1759-1768
  • 29 Burchell B, Lockley D J, Staines A, Uesawa Y, Coughtrie M W. Substrate specificity of human hepatic udp-glucuronosyltransferases.  Methods Enzymol. 2005;  400 46-57
  • 30 Williams J A, Hyland R, Jones B C, Smith D A, Hurst S, Goosen T C, Peterkin V, Koup J R, Ball S E. Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios.  Drug Metab Dispos. 2004;  32 1201-1208
  • 31 Sahai J, Gallicano K, Pakuts A, Cameron D W. Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.  J Infect Dis. 1994;  169 1103-1107
  • 32 Lee B L, Tauber M G, Sadler B, Goldstein D, Chambers H F. Atovaquone inhibits the glucuronidation and increases the plasma concentrations of zidovudine.  Clin Pharmacol Ther. 1996;  59 14-21
  • 33 Kiang T K, Ensom M H, Chang T K. UDP-glucuronosyltransferases and clinical drug-drug interactions.  Pharmacol Ther. 2005;  106 97-132
  • 34 Ebert U, Thong N Q, Oertel R, Kirch W. Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects.  Eur J Clin Pharmacol. 2000;  56 299-304
  • 35 van der Lee M J, Dawood L, ter Hofstede H J, de Graaff-Teulen M J, van Ewijk-Beneken Kolmer E W, Caliskan-Yassen N, Koopmans P P, Burger D M. Lopinavir/ritonavir reduces lamotrigine plasma concentrations in healthy subjects.  Clin Pharmacol Ther. 2006;  80 159-168
  • 36 Ni Y, Turner D, Yates K, Tizard I. Isolation and characterization of structural components of Aloe vera L. leaf pulp.  Int Immunopharmacol. 2004;  4 1745-1755
  • 37 Dagne E, Bisrat D, Viljoen A, Van Wyk B. Chemistry of Aloe species.  Curr Org Chem. 2000;  4 1055-1078
  • 38 Shia C S, Juang S H, Tsai S Y, Chang P H, Kuo S C, Hou Y C, Chao P D. Metabolism and pharmacokinetics of anthraquinones in Rheum palmatum in rats and ex vivo antioxidant activity.  Planta Med. 2009;  75 1386-1392
  • 39 Neto C C. Cranberry and its phytochemicals: a review of in vitro anticancer studies.  J Nutr. 2007;  137 186S
  • 40 Hakkinen S H, Karenlampi S O, Heinonen I M, Mykkanen H M, Torronen A R. Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries.  J Agric Food Chem. 1999;  47 2274-2279
  • 41 Zhang L, Zuo Z, Lin G. Intestinal and hepatic glucuronidation of flavonoids.  Mol Pharm. 2007;  4 833-845
  • 42 Chen Y, Xie S, Chen S, Zeng S. Glucuronidation of flavonoids by recombinant UGT1A3 and UGT1A9.  Biochem Pharmacol. 2008;  76 416-425
  • 43 Oliveira E J, Watson D G. In vitro glucuronidation of kaempferol and quercetin by human UGT-1A9 microsomes.  FEBS Lett. 2000;  471 1-6
  • 44 Williams J A, Ring B J, Cantrell V E, Campanale K, Jones D R, Hall S D, Wrighton S A. Differential modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1)-catalyzed estradiol-3-glucuronidation by the addition of UGT1A1 substrates and other compounds to human liver microsomes.  Drug Metab Dispos. 2002;  30 1266-1273
  • 45 Mohamed M F, Frye R F. Inhibition of intestinal and hepatic glucuronidation of mycophenolic acid by Ginkgo biloba extract and flavonoids.  Drug Metab Dispos. 2010;  38 270
  • 46 Sun X Y, Plouzek C A, Henry J P, Wang T T, Phang J M. Increased UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells.  Cancer Res. 1998;  58 2379-2384
  • 47 Turgeon D, Carrier J S, Levesque E, Hum D W, Belanger A. Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members.  Endocrinology. 2001;  142 778-787
  • 48 Van der Logt E, Roelofs H, Nagengast F, Peters W. Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens.  Carcinogenesis. 2003;  24 1651
  • 49 Iyer L, King C D, Whitington P F, Green M D, Roy S K, Tephly T R, Coffman B L, Ratain M J. Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes.  J Clin Invest. 1998;  101 847-854
  • 50 King C D, Rios G R, Green M D, Tephly T R. UDP-glucuronosyltransferases.  Curr Drug Metab. 2000;  1 143-161
  • 51 Kuehl G E, Murphy S E. N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases.  Drug Metab Dispos. 2003;  31 1361-1368
  • 52 Moon Y J, Wang L, DiCenzo R, Morris M E. Quercetin pharmacokinetics in humans.  Biopharm Drug Dispos. 2008;  29 205-217
  • 53 Wang Y, Catana F, Yang Y, Roderick R, van Breemen R B. An LC-MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine.  J Agric Food Chem. 2002;  50 431-435
  • 54 Brill S S, Furimsky A M, Ho M N, Furniss M J, Li Y, Green A G, Bradford W W, Green C E, Kapetanovic I M, Iyer L V. Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms.  J Pharm Pharmacol. 2006;  58 469-479
  • 55 Iwuchukwu O F, Nagar S. Resveratrol (trans-resveratrol, 3,5,4′-trihydroxy-trans-stilbene) glucuronidation exhibits atypical enzyme kinetics in various protein sources.  Drug Metab Dispos. 2008;  36 322-330
  • 56 de Santi C, Pietrabissa A, Mosca F, Pacifici G M. Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver.  Xenobiotica. 2000;  30 1047-1054
  • 57 Marin F R, Ortuno A, Benavente-Garcia O, Del Rio J A. Distribution of flavone glycoside diosmin in Hyssopus officinalis plants: changes during growth.  Planta Med. 1998;  64 181-182
  • 58 del Bano M J, Lorente J, Castillo J, Benavente-Garcia O, Marin M P, Del Rio J A, Ortuno A, Ibarra I. Flavonoid distribution during the development of leaves, flowers, stems, and roots of Rosmarinus officinalis. postulation of a biosynthetic pathway.  J Agric Food Chem. 2004;  52 4987-4992
  • 59 Benavente-Garcia O, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity.  J Agric Food Chem. 2008;  56 6185-6205
  • 60 Cesarone M R, Belcaro G, Pellegrini L, Ledda A, Vinciguerra G, Ricci A, Di Renzo A, Ruffini I, Gizzi G, Ippolito E, Fano F, Dugall M, Acerbi G, Cornelli U, Hosoi M, Cacchio M. Venoruton vs. Daflon: evaluation of effects on quality of life in chronic venous insufficiency.  Angiology. 2006;  57 131-138
  • 61 Serra H, Mendes T, Bronze M R, Simplicio A L. Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones.  Bioorg Med Chem. 2008;  16 4009-4018
  • 62 Perego R, Beccaglia P, Angelini M, Villa P, Cova D. Pharmacokinetic studies of diosmin and diosmetin in perfused rat liver.  Xenobiotica. 1993;  23 1345-1352
  • 63 Fleming T. PDR for herbal medicines. New York; Thomson Reuters 2000
  • 64 Jia C, Shi H, Jin W, Zhang K, Jiang Y, Zhao M, Tu P. Metabolism of echinacoside, a good antioxidant, in rats: isolation and identification of its biliary metabolites.  Drug Metab Dispos. 2009;  37 431
  • 65 Mohamed M F, Tseng T, Frye R F. Inhibitory effects of commonly used herbal extracts on UGT1A1 enzyme activity.  Xenobiotica. 2010;  40 663-669
  • 66 Corzo-Martínez M, Corzo N, Villamiel M. Biological properties of onions and garlic.  Trends Food Sci Technol. 2007;  18 609-625
  • 67 Gwilt P R, Lear C L, Tempero M A, Birt D D, Grandjean A C, Ruddon R W, Nagel D L. The effect of garlic extract on human metabolism of acetaminophen.  Cancer Epidemiol Biomarkers Prev. 1994;  3 155-160
  • 68 Chan P C, Xia Q, Fu P P. Ginkgo biloba leave extract: biological, medicinal, and toxicological effects.  J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2007;  25 211-244
  • 69 Tukey R H, Strassburg C P. Human UDP-glucuronosyltransferases: metabolism, expression, and disease.  Annu Rev Pharmacol Toxicol. 2000;  40 581-616
  • 70 Allison A C, Eugui E M. Mechanisms of action of mycophenolate mofetil in preventing acute and chronic allograft rejection.  Transplantation. 2005;  80 S181-S190
  • 71 Heatwole C, Ciafaloni E. Mycophenolate mofetil for myasthenia gravis: a clear and present controversy.  Neuropsychiatr Dis Treat. 2008;  4 1203-1209
  • 72 Picard N, Ratanasavanh D, Premaud A, Le Meur Y, Marquet P. Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism.  Drug Metab Dispos. 2005;  33 139-146
  • 73 Hellum B H, Hu Z, Nilsen O G. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes.  Basic Clin Pharmacol Toxicol. 2007;  100 23-30
  • 74 Staatz C E, Tett S E. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients.  Clin Pharmacokinet. 2007;  46 13-58
  • 75 Chen C, Chiou W, Zhang J. Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium.  Acta Pharmacol Sin. 2008;  29 1103-1108
  • 76 Yang L, Deng Y, Xu S, Zeng X. In vivo pharmacokinetic and metabolism studies of ginsenoside Rd.  J Chromatogr B Analyt Technol Biomed Life Sci. 2007;  854 77-84
  • 77 Cai Z, Qian T, Wong R, Jiang Z. Liquid chromatography–electrospray ionization mass spectrometry for metabolism and pharmacokinetic studies of ginsenoside Rg3.  Anal Chim Acta. 2003;  492 283-293
  • 78 Lee L S, Wise S D, Chan C, Parsons T L, Flexner C, Lietman P S. Possible differential induction of phase 2 enzyme and antioxidant pathways by American ginseng, Panax quinquefolius.  J Clin Pharmacol. 2008;  48 599
  • 79 Nassiri-Asl M, Hosseinzadeh H. Review of the pharmacological effects of Vitis vinifera (Grape) and its bioactive compounds.  Phytother Res. 2009;  23 1197-1204
  • 80 Tsang C, Auger C, Mullen W, Bornet A, Rouanet J M, Crozier A, Teissedre P L. The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats.  Br J Nutr. 2007;  94 170-181
  • 81 Cabrera C, Artacho R, Giménez R. Beneficial effects of green tea–a review.  J Am Coll Nutr. 2006;  25 79
  • 82 Gupta S, Saha B, Giri A K. Comparative antimutagenic and anticlastogenic effects of green tea and black tea: a review.  Mutat Res. 2002;  512 37-65
  • 83 Feng W Y. Metabolism of green tea catechins: an overview.  Curr Drug Metab. 2006;  7 755-809
  • 84 Lu H, Meng X, Li C, Sang S, Patten C, Sheng S, Hong J, Bai N, Winnik B, Ho C T, Yang C S. Glucuronides of tea catechins: enzymology of biosynthesis and biological activities.  Drug Metab Dispos. 2003;  31 452-461
  • 85 Bu-Abbas A, Clifford M N, Walker R, Ioannides C. Contribution of caffeine and flavanols in the induction of hepatic phase II activities by green tea.  Food Chem Toxicol. 1998;  36 617-621
  • 86 Zhu B T, Taneja N, Loder D P, Balentine D A, Conney A H. Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone.  J Steroid Biochem Mol Biol. 1998;  64 207-215
  • 87 Court M H. Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases.  Methods Enzymol. 2005;  400 104-116
  • 88 Foster D R, Sowinski K M, Chow H H, Overholser B R. Limited sampling strategies to estimate exposure to the green tea polyphenol, epigallocatechin gallate, in fasting and fed conditions.  Ther Drug Monit. 2007;  29 835-842
  • 89 Fisher M B, Labissiere G. The role of the intestine in drug metabolism and pharmacokinetics: an industry perspective.  Curr Drug Metab. 2007;  8 694-699
  • 90 Mirkov S, Komoroski B J, Ramirez J, Graber A Y, Ratain M J, Strom S C, Innocenti F. Effects of green tea compounds on irinotecan metabolism.  Drug Metab Dispos. 2007;  35 228
  • 91 Dahmer S, Scott E. Health effects of hawthorn.  Am Fam Physician. 2010;  81 465-468
  • 92 Zuo Z, Zhang L, Zhou L, Chang Q, Chow M. Intestinal absorption of hawthorn flavonoids–in vitro, in situ and in vivo correlations.  Life Sci. 2006;  79 2455-2462
  • 93 Blumenthal M. Herbal Medicine: Expanded Commission E Monographs. Newton, MA; Integrative Medicine Communications 2000
  • 94 Kuhnle G, Spencer J P, Schroeter H, Shenoy B, Debnam E S, Srai S K, Rice-Evans C, Hahn U. Epicatechin and catechin are O-methylated and glucuronidated in the small intestine.  Biochem Biophys Res Commun. 2000;  277 507-512
  • 95 Obolskiy D, Pischel I, Siriwatanametanon N, Heinrich M. Garcinia mangostana L.: a phytochemical and pharmacological review.  Phytother Res. 2009;  23 1047-1065
  • 96 Bumrungpert A, Kalpravidh R W, Suksamrarn S, Chaivisuthangkura A, Chitchumroonchokchai C, Failla M L. Bioaccessibility, biotransformation, and transport of alpha-mangostin from Garcinia mangostana (Mangosteen) using simulated digestion and Caco-2 human intestinal cells.  Mol Nutr Food Res. 2009;  53 (Suppl. 1) S54-S61
  • 97 Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease.  Am J Gastroenterol. 2004;  93 139-143
  • 98 Dhiman R, Chawla Y. Herbal medicines for liver diseases.  Dig Dis Sci. 2005;  50 1807-1812
  • 99 Miranda S R, Lee J K, Brouwer K L, Wen Z, Smith P C, Hawke R L. Hepatic metabolism and biliary excretion of silymarin flavonolignans in isolated perfused rat livers: role of multidrug resistance-associated protein 2 (Abcc2).  Drug Metab Dispos. 2008;  36 2219-2226
  • 100 Hoh C, Boocock D, Marczylo T, Singh R, Berry D P, Dennison A R, Hemingway D, Miller A, West K, Euden S, Garcea G, Farmer P B, Steward W P, Gescher A J. Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences.  Clin Cancer Res. 2006;  12 2944-2950
  • 101 Venkataramanan R, Ramachandran V, Komoroski B J, Zhang S, Schiff P L, Strom S C. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures.  Drug Metab Dispos. 2000;  28 1270-1273
  • 102 Sridar C, Goosen T C, Kent U M, Williams J A, Hollenberg P F. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases.  Drug Metab Dispos. 2004;  32 587-594
  • 103 van Erp N P, Baker S D, Zhao M, Rudek M A, Guchelaar H J, Nortier J W, Sparreboom A, Gelderblom H. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.  Clin Cancer Res. 2005;  11 7800-7806
  • 104 Potterat O, Hamburger M. Morinda citrifolia (Noni) fruit–phytochemistry, pharmacology, safety.  Planta Med. 2007;  73 191-199
  • 105 Mahfoudh A, Ismail N, Ismail S, Hussin A. In vitro ex vivo assessment of Morinda citrifolia on drug metabolizing enzymes in spontaneously hypertensive rats.  Pharm Biol. 2009;  47 1-9
  • 106 Nielsen I, Williamson G. Review of the factors affecting bioavailability of soy isoflavones in humans.  Nutr Cancer. 2007;  57 1-10
  • 107 Doerge D R, Chang H C, Churchwell M I, Holder C L. Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography-mass spectrometry.  Drug Metab Dispos. 2000;  28 298-307
  • 108 Pfeiffer E, Treiling C R, Hoehle S I, Metzler M. Isoflavones modulate the glucuronidation of estradiol in human liver microsomes.  Carcinogenesis. 2005;  26 2172-2178
  • 109 Park S Y, Wilkens L R, Franke A A, Le Marchand L, Kakazu K K, Goodman M T, Murphy S P, Henderson B E, Kolonel L N. Urinary phytoestrogen excretion and prostate cancer risk: a nested case-control study in the Multiethnic Cohort.  Br J Cancer. 2009;  101 185-191
  • 110 Anderson G D, Rosito G, Mohustsy M A, Elmer G W. Drug interaction potential of soy extract and Panax ginseng.  J Clin Pharmacol. 2003;  43 643-648
  • 111 Takimoto C H, Glover K, Huang X, Hayes S A, Gallot L, Quinn M, Jovanovic B D, Shapiro A, Hernandez L, Goetz A, Llorens V, Lieberman R, Crowell J A, Poisson B A, Bergan R C. Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer.  Cancer Epidemiol Biomarkers Prev. 2003;  12 1213-1221
  • 112 Froyen E B, Reeves J L, Mitchell A E, Steinberg F M. Regulation of phase II enzymes by genistein and daidzein in male and female Swiss Webster mice.  J Med Food. 2009;  12 1227-1237
  • 113 Gaster B, Holroyd J. St John's wort for depression: a systematic review.  Arch Intern Med. 2000;  160 152
  • 114 Butterweck V, Schmidt M. St. John's wort: role of active compounds for its mechanism of action and efficacy.  Wien Med Wochenschr. 2007;  157 356-361
  • 115 Volak L. Role for protein kinase C delta in the functional activity of human UGT1A6: implications for drug-drug interactions between PKC inhibitors and UGT1A6.  Xenobiotica. 2010;  40 306-318
  • 116 Schulz H U, Schurer M, Bassler D, Weiser D. Investigation of pharmacokinetic data of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin revealed from single and multiple oral dose studies with a Hypericum extract containing tablet in healthy male volunteers.  Arzneimittelforschung. 2005;  55 561-568
  • 117 Hu Z P, Yang X X, Chen X, Cao J, Chan E, Duan W, Huang M, Yu X Q, Wen J Y, Zhou S F. A mechanistic study on altered pharmacokinetics of irinotecan by St. John's wort.  Curr Drug Metab. 2007;  8 157-171
  • 118 Collins J M. Inter-species differences in drug properties.  Chem Biol Interact. 2001;  134 237-242
  • 119 Boocock D J, Maggs J L, Brown K, White I N, Park B K. Major inter-species differences in the rates of O-sulphonation and O-glucuronylation of alpha-hydroxytamoxifen in vitro: a metabolic disparity protecting human liver from the formation of tamoxifen-DNA adducts.  Carcinogenesis. 2000;  21 1851-1858
  • 120 Patocka J, Jakl J. Biomedically relevant chemical constituents of Valeriana officinalis.  J Appl Biomed. 2010;  8 11-18
  • 121 Alkharfy K M, Frye R F. Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro.  Xenobiotica. 2007;  37 113-123
  • 122 Anderson G D, Elmer G W, Kantor E D, Templeton I E, Vitiello M V. Pharmacokinetics of valerenic acid after administration of valerian in healthy subjects.  Phytother Res. 2005;  19 801-803
  • 123 Kidd P. Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts.  Altern Med Rev. 2009;  14 226-246

Dr. Reginald F. Frye, Associate Professor

Department of Pharmacotherapy and Translational Research
College of Pharmacy
University of Florida

P. O. Box 100486

Gainesville, FL 32610

USA

Phone: +1 352 273 5453

Fax: +1 352 273 6121

Email: frye@cop.ufl.edu

    >