The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity

Drug Metabolism and Disposition

Volumn 42, Issue 10, 2014, Pages 1611-1616

  Kawaguchi Suzuki, Marina ^a,b   Frye, Reginald F ^a,b   Zhu, Hao Jie ^e   Brinda, Bryan J ^a   Chavin, Kenneth D ^d   Bernstein, Hilary J ^c   Markowitz, John S ^a,b  

^a Department of Pharmacotherapy and Translational Research ^*  (United States)

^b UNIVERSITY OF FLORIDA   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

^d Division of Transplant Surgery   (United States)

^e MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CAFFEINE; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DEXTROMETHORPHAN; ENZYME INHIBITOR; GUAIFENESIN; ISOSILYBIN B; MIDAZOLAM; SILIBININ; SILYBIN A; SILYBIN B; SILYBUM MARIANUM EXTRACT; SILYMARIN; TOLBUTAMIDE; UNCLASSIFIED DRUG; CYTOCHROME P450 INHIBITOR; ISOSILYBIN A; PLANT EXTRACT;

ADULT; AREA UNDER THE CURVE; ARTICLE; BIOEQUIVALENCE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG EFFECT; DRUG METABOLISM; ENZYME ACTIVITY; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN EXPERIMENT; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHYTOCHEMISTRY; PLASMA CONCENTRATION-TIME CURVE; SINGLE DRUG DOSE; TANDEM MASS SPECTROMETRY; ANALOGS AND DERIVATIVES; ANALYSIS; BLOOD; CHEMISTRY; CLINICAL TRIAL; DIET SUPPLEMENTATION; HERB DRUG INTERACTION; METABOLISM; SILYBUM MARIANUM; YOUNG ADULT;

CAFFEINE; CYTOCHROME P-450 ENZYME INHIBITORS; CYTOCHROME P-450 ENZYME SYSTEM; DEXTROMETHORPHAN; DIETARY SUPPLEMENTS; FEMALE; HERB-DRUG INTERACTIONS; HUMANS; MALE; MIDAZOLAM; MILK THISTLE; PLANT EXTRACTS; SILYMARIN; TOLBUTAMIDE; YOUNG ADULT;

EID: 84907459077     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.114.057232     Document Type: Article

References (43)

1. Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, Böcker RH, Beckurts KT, Lang W, Hunz M, and Fuhr U (2000) Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 86:250-256.
2. Brantley SJ, Oberlies NH, Kroll DJ, and Paine MF (2010) Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J Pharmacol Exp Ther 332:1081-1087.
3. Brinda BJ, Zhu HJ, and Markowitz JS (2012) A sensitive LC-MS/MS assay for the simultaneous analysis of the major active components of silymarin in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 902:1-9.
4. Chien JY, Lucksiri A, Ernest CS, 2nd, Gorski JC, Wrighton SA, and Hall SD (2006) Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole. Drug Metab Dispos 34:1208-1219.
5. Choi YH, Chin YW, and Kim YG (2011) Herb-drug interactions: focus on metabolic enzymes and transporters. Arch Pharm Res 34:1843-1863.
6. Deng JW, Shon JH, Shin HJ, Park SJ, Yeo CW, Zhou HH, Song IS, and Shin JG (2008) Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res 25:1807-1814.
7. DiCenzo R, Shelton M, Jordan K, Koval C, Forrest A, Reichman R, and Morse G (2003) Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy 23:866-870.
8. Flaig TW, Gustafson DL, Su LJ, Zirrolli JA, Crighton F, Harrison GS, Pierson AS, Agarwal R, and Glodé LM (2007) A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs 25:139-146.
9. Fuhr U, Beckmann-Knopp S, Jetter A, Lück H, and Mengs U (2007) The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med 73:1429-1435.
10. Guengerich FP (2001) Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 14:611-650.
11. Gurley B, Hubbard MA, Williams DK, Thaden J, Tong Y, Gentry WB, Breen P, Carrier DJ, and Cheboyina S (2006a) Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol 46:201-213.
12. Gurley BJ, Barone GW, Williams DK, Carrier J, Breen P, Yates CR, Song PF, Hubbard MA, Tong Y, and Cheboyina S (2006b) Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos 34:69-74.
13. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Carrier J, Khan IA, Edwards DJ, and Shah A (2004) In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 76:428-440.
14. Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, and Battu SK (2008) Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 52:755-763.
15. Han Y, Guo D, Chen Y, Chen Y, Tan ZR, and Zhou HH (2009) Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur J Clin Pharmacol 65:585-591.
16. Heim M and Meyer UA (1990) Genotyping of poor metabolisers of debrisoquine by allelespecific PCR amplification. Lancet 336:529-532.
17. Javed S, Kohli K, and Ali M (2011) Reassessing bioavailability of silymarin. Altern Med Rev 16: 239-249.
18. Karunathilake NP, Frye RF, Stavropoulos MF, Herman MA, and Hastie BA (2012) A preliminary study on the effects of self-reported dietary caffeine on pain experience and postoperative analgesia. J Caffeine Res 2:159-166.
19. Kroll DJ, Shaw HS, and Oberlies NH (2007) Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther 6:110-119.
20. Leber HW and Knauff S (1976) Influence of silymarin on drug metabolizing enzymes in rat and man. Arzneimittelforschung 26:1603-1605.
21. Lindstrom A, Ooyen C, Lynch M, and Blumenthal M (2013) Herb supplement sales increase 5.5% in 2012: herbal supplement sales rise for 9th consecutive year; turmeric sales jump 40% in natural channel. HerbalGram 99:60-65.
22. Loguercio C and Festi D (2011) Silybin and the liver: from basic research to clinical practice. World J Gastroenterol 17:2288-2301.
23. Mills E, Wilson K, Clarke M, Foster B, Walker S, Rachlis B, DeGroot N, Montori VM, Gold W, and Phillips E, et al. (2005) Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. Eur J Clin Pharmacol 61:1-7.
24. Moltó J, Valle M, Miranda C, Cedeño S, Negredo E, and Clotet B (2012) Effect of milk thistle on the pharmacokinetics of darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother 56:2837-2841.
25. National Toxicology Program (2011) Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies). Natl Toxicol Program Tech Rep Ser 565:1-177.
26. Nolin TD, Frye RF, Le P, Sadr H, Naud J, Leblond FA, Pichette V, and Himmelfarb J (2009) ESRD impairs nonrenal clearance of fexofenadine but not midazolam. J Am Soc Nephrol 20: 2269-2276.
27. Piscitelli SC, Formentini E, Burstein AH, Alfaro R, Jagannatha S, and Falloon J (2002) Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 22: 551-556.
28. Rajnarayana K, Reddy MS, Vidyasagar J, and Krishna DR (2004) Study on the influence of silymarin pretreatment on metabolism and disposition of metronidazole. Arzneimittelforschung 54:109-113.
29. Rao BN, Srinivas M, Kumar YS, and Rao YM (2007) Effect of silymarin on the oral bioavailability of ranitidine in healthy human volunteers. Drug Metabol Drug Interact 22: 175-185.
30. Ring BJ, Patterson BE, Mitchell MI, Vandenbranden M, Gillespie J, Bedding AW, Jewell H, Payne CD, Forgue ST, and Eckstein J, et al. (2005) Effect of tadalafil on cytochrome P450 3A4-mediated clearance: studies in vitro and in vivo. Clin Pharmacol Ther 77:63-75.
31. Schrieber SJ, Hawke RL, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, Afdhal NH, Navarro VJ, and Meyers CM, et al. (2011) Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C. Drug Metab Dispos 39: 2182-2190.
32. Schrieber SJ, Wen Z, Vourvahis M, Smith PC, Fried MW, Kashuba AD, and Hawke RL (2008) The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic fatty liver disease and correlates with plasma caspase-3/7 activity. Drug Metab Dispos 36: 1909-1916.
33. Shi S and Klotz U (2012) Drug interactions with herbal medicines. Clin Pharmacokinet 51: 77-104.
34. Sridar C, Goosen TC, Kent UM, Williams JA, and Hollenberg PF (2004) Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 32:587-594.
35. Tomalik-Scharte D, Jetter A, Kinzig-Schippers M, Skott A, Sörgel F, Klaassen T, Kasel D, Harlfinger S, Doroshyenko O, and Frank D, et al. (2005) Effect of propiverine on cytochrome P450 enzymes: a cocktail interaction study in healthy volunteers. Drug Metab Dispos 33: 1859-1866.
36. U.S. Department of Health and Human Services and Food and Drug Administration Center for Drug Evaluation and Research (CDER) (2012) Guidance for Industry Drug Interaction Studies-Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations, Rockville, MD.
37. van Erp NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW, Sparreboom A, and Gelderblom H (2005) Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 11:7800-7806.
38. Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, and Strom SC (2000) Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28:1270-1273.
39. Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, and Hall SD (2001) The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 70:317-326.
40. Wohlfarth A, Naue J, Lutz-Bonengel S, Dresen S, and Auwärter V (2012) Cocktail approach for in vivo phenotyping of 5 major CYP450 isoenzymes: development of an effective sampling, extraction, and analytical procedure and pilot study with comparative genotyping. J Clin Pharmacol 52:1200-1214.
41. Zanger UM and Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138: 103-141.
42. Zhu HJ, Brinda BJ, Chavin KD, Bernstein HJ, Patrick KS, and Markowitz JS (2013) An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study. Drug Metab Dispos 41:1679-1685.
43. Zuber R, Modrianský M, Dvorák Z, Rohovský P, Ulrichová J, Simánek V, and Anzenbacher P (2002) Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 16:632-638.