Introduction: This survey aims to identify herb-chemotherapeutic drug combinations in a defined group of cancer patients and to explore possible clinical consequences of these combinations. Methods: Herb-chemotherapeutic drug combinations were identified among adult cancer patients, and clinical consequences of the combinations were explored by literature searches in medical databases on possible mutual effects on similar cytochrome P-450 metabolising enzymes (CYPs) and/or the P-glycoprotein (P-gp) transporter. Results: Among 42 cancer patients using herbal remedies concurrently with chemotherapy, 136 two-agent herb-drug combinations were registered and 47 different potential herb-drug interactions were identified on the level of CYP metabolism and P-gp transport in vitro. Garlic, ginger, green tea and noni juice were the herbal remedies most frequently used in such combinations. For 48 % of the herbal remedies identified no literature data exist on their interaction potentials. Clinical studies were available for four herbal remedies only. Minor clinical potential for CYP interactions in humans was indicated for green tea and Echinacea. P-gp interactions were only investigated for garlic, which showed a significant interaction potential both in vivo and in vitro. Conclusion: The large number of in vitro potential herb-drug interactions identified urge for more clinical pharmacokinetic interaction studies in humans.
Eisenberg DM , Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998;280:1569-1575.
2.
Boon HS, Olatunde F., Zick SMTrends in complementary/alternative medicine use by breast cancer survivors: comparing survey data from 1998 and 2005. BMC Womens Health . 2007;7:4.
3.
Hall SD, Wang Z., Huang SM, et al. The interaction between St John's wort and an oral contraceptive . Clin Pharmacol Ther. 2003;74:525-535.
4.
Bauer S., Stormer E., Johne A., et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol. 2003;55:203-211.
5.
Singh SR, Levine MAH.Potential interactions between pharmaceuticals and natural health products in Canada. J Clin Pharmacol. 2007 ;47:249-258.
6.
Bush TM, Rayburn KS, Holloway SW, et al. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Altern Ther Health Med. 2007;13:30-35.
7.
Elmer GW, Lafferty WE, Tyree PT, Lind BKPotential interactions between complementary/alternative products and conventional medicines in a Medicare population. Ann Pharmacother. 2007;41:1617-1624.
8.
Malekzadeh F. , Rose C., Ingvar C., Jernstrom H.Naturläkemedel och hormonpreparat - potentiell risk för bröstcancerpatienter. Studie kartlägger bruk av medel som kanske motverkar behandlingen. Lakartidningen. 2005 ;102:3226-3231.
9.
Eschiti VSLesson from comparison of CAM use by women with female-specific cancers to others: It's time to focus on interaction risks with CAM therapies. Integr Cancer Ther. 2007;6:313-344.
10.
Engdal S., Steinsbekk A., Klepp O., Nilsen OGHerbal use among cancer patients during palliative or curative chemotherapy treatment in Norway. Support Care Cancer. 2008;16:763-769.
11.
World Health Organization.National Policy on Traditional Medicine and Regulation of Herbal Medicines - Report of a WHO Global Survey. Geneva, Switzerland: World Health Organization; 2005.
12.
Netsch MI, Gutmann H., Schmidlin CB, Aydogan C., Drewe J.Induction of CYP1A by green tea extract in human intestinal cell lines . Planta Med. 2006;72:514-520.
13.
Yang SP, Raner GMCytochrome P450 expression and activities in human tongue cells and their modulation by green tea extract. Toxicol Appl Pharmacol . 2005;202:140-150.
14.
Muto S., Fujita KI, Yamazaki Y., Kamataki T.Inhibition by green tea catechins of metabolic activation of procarcinogens by human cytochrome P450. Mutat Res. 2001;479:197-206.
15.
Wang E.-J. Barecki-Roach M., Johnson WWElevation of P-glycoprotein function by a catechin in green tea. Biochem Biophys Res Commun. 2002;297:412-418.
16.
Foster BC, Foster MS, Vandenhoek S., et al. An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic. J Pharm Pharm Sci. 2001 ;4:176-184.
17.
Greenblatt DJ, Leigh-Pemberton RA, von Moltke LLIn vitro interactions of water-soluble garlic components with human cytochromes p450. J Nutr.2006;136:806S-809S.
18.
Yale SH, Glurich I.Analysis of the inhibitory potential of Ginkgo biloba, echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med. 2005;11:433-439.
19.
Modarai M., Gertsch J., Suter A., Heinrich M., Kortenkamp A.Cytochrome P450 inhibitory action of echinacea preparations differs widely and co-varies with alkylamide content. J Pharm Pharmacol . 2007;59:567-573.
20.
Hellum BH, Nilsen OGIn vitro inhibition of CYP3A4 metabolism and P-glycoprotein mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol . In press.
21.
Budzinski JW , Foster BC, Trudeau VL, Drouin CE, Bafi-Yeboa N., Arnason JTThe interaction of selected phytochemicals, HIV drugs, and commercial-source herbal teas and capsules with human cytochrome P450 3A4 and P-glycoprotein. Pharm Biol.2008 ;46:53-65.
22.
Lefebvre T. , Foster BC, Drouin CE, Krantis A., Livesey JF, Jordan SAIn vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharm Sci.2004;7:265-273.
23.
Hellum BH, Hu Z., Nilsen OGThe induction of CYP1A2, CYP2D6, and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol . 2007;100:23-30.
24.
Hellum BH, Nilsen OGIn vitro inhibition of CYP3A4 metabolism and P-glycoprotein mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol.2008;102:466-475.
25.
Anderson GD , Rosito G., Mohustsy MA, Elmer GWDrug interaction potential of soy extract and Panax ginseng. J Clin Pharmacol . 2003;43:643-648.
26.
Foster BC, Vandenhoek S., Hana J., et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine.2003;10: 334-342.
27.
Li Y., Mezei O., Shay NFHuman and murine hepatic sterol-12-alpha-hydroxylase and other xenobiotic metabolism mRNA are upregulated by soy isoflavones. J Nutr . 2007;137: 1705-1712.
28.
Green AK, Barnes DM, Karasov WHA new method to measure intestinal activity of P-glycoprotein in avian and mammalian species. J Comp Physiol [B]. 2005;175:57-66.
29.
Brandin H., Viitanen E., Myrberg O., Arvidsson AKEffects of herbal medicinal products and food supplements on induction of CYP1A2, CYP3A4, and MDR1 in the human colon carcinoma cell line LS180. Phytother Res. 2007;21:239-244.
30.
Raucy JLRegulation of CYP3A4 expression in human hepatocytes by pharmaceuticals and natural products. Drug Metab Dispos. 2003 ;31:533-539.
31.
Scott IM, Leduc RI, Burt AJ, Marles RJ, Arnason JT, Foster BCThe inhibition of human cytochrome P450 by ethanol extracts of NorthAmerican botanicals. Pharm Biol. 2006;44:315-327.
32.
Engdal S., Nilsen OGInhibition of P-glycoprotein in Caco-2 cells: effects of herbal remedies frequently used by cancer patients. Xenobiotica. 2008 ;36:559-573.
33.
Matsuda K., Nishimura Y., Kurata N., Iwase M., Yasuhara H.Effects of continuous ingestion of herbal teas on intestinal CYP3A in the rat. J Pharmacol Sci. 2007;103:214-221.
34.
Cox MC, Low J., Lee J., et al. Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel. Clin Cancer Res. 2006;12:4636-4640.
35.
Chow HH, Hakim IA, Vining DR, et al. Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol Biomarkers Prev . 2006;15: 2473-2476.
36.
Donovan JL, Chavin KD, Devane CL, et al. Green tea (Camellia sinensis) extract does not alter cytochrome p450 3A4 or 2D6 activity in healthy volunteers. Drug Metab Dispos. 2004;32:906-908.
37.
Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther.2005;77:415-426.
38.
Donovan JL, DeVane CL, Chavin KD, et al. Multiple nighttime doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos. 2004 ;32:1333-1336.
39.
Piscitelli SC, Burstein AH, Welden N., Gallicano KD, Falloon J.The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis. 2002;34:234-238.
40.
Markowitz JS , DeVane CL, Chavin KD, Taylor RM, Ruan Y., Donovan JLEffects of garlic (Allium sativum L) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers. Clin Pharmacol Ther. 2003;74:170-177.
41.
Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba. Drugs Aging. 2005;22: 525-539.
42.
Gorski JC, Huang SM, Pinto A., et al. The effect of echinacea (echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther. 2004;75:89-100.
43.
Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther.2004;76:428-440.
44.
Balayssac D. , Authier N., Cayre A., Coudore F.Does inhibition of P-glycoprotein lead to drug-drug interactions? Toxicol Lett. 2005 ;156:319-329.
45.
Scripture CD , Sparreboom A., Figg WDModulation of cytochrome P450 activity: Implications for cancer therapy. Lancet Oncol . 2005;6:780-789.
46.
Kleeberg UR , Suciu S., Brocker EB, et al. Final results of the EORTC 18871/DKG 80-1 randomized phase III trial. rIFNalpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer.2004;40:390-402.
