{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:49:04Z","timestamp":1792802944415,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":1071,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>Silymarin, derived from the milk thistle plant<jats:italic>Silybum marianum<\/jats:italic>, is widely used for self\u2010treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose\u2010exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well\u2010compensated, chronic noncirrhotic HCV who failed interferon\u2010based therapy were randomized 3:1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg silymarin were administered every 8 hours for 7 days. Steady\u2010state exposures for silybin A and silybin B increased 11\u2010fold and 38\u2010fold, respectively, with a 5\u2010fold increase in dose, suggesting nonlinear pharmacokinetics. No drug\u2010related adverse events were reported, and no clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.<\/jats:p>","DOI":"10.1177\/0091270009347475","type":"journal-article","created":{"date-parts":[[2009,10,20]],"date-time":"2009-10-20T01:31:26Z","timestamp":1256002286000},"page":"434-449","source":"Crossref","is-referenced-by-count":129,"title":["Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C"],"prefix":"10.1002","volume":"50","author":[{"given":"Roy L.","family":"Hawke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Schrieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tedi A.","family":"Soule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Rajender","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdus S.","family":"Wahed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Belle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nezam H.","family":"Afdhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor J.","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Doo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Fried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The SyNCH Trial Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020047"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06102-5"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMct061675"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-002-0034-y"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.18.1569"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05993.x"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1998.00139.x"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22044"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1039\/b300099k"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.811"},{"key":"e_1_2_5_12_2","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0090-9556(24)11798-9","article-title":"Chemoenzymatic preparation of silybin beta\u2010glucuronides and their biological evaluation","volume":"28","author":"Kren V","year":"2000","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_5_13_2","doi-asserted-by":"crossref","first-page":"6800","DOI":"10.4049\/jimmunol.163.12.6800","article-title":"Silymarin suppresses TNF\u2010induced activation of NF\u2010kappa B, c\u2010Jun N\u2010terminal kinase, and apoptosis","volume":"163","author":"Manna SK","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00239-3"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2008.00971.x"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00148-9"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2005.00636.x"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.017566"},{"key":"e_1_2_5_19_2","first-page":"964","article-title":"Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients","volume":"42","author":"Schandalik R","year":"1992","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.021790"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03189986"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03188811"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04138.x"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.02.038"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2008.01833.x"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.07.072"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.019604"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-006-9019-2"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.053"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365528209182242"},{"key":"e_1_2_5_31_2","first-page":"283","article-title":"Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers","volume":"22","author":"Lang I","year":"1990","journal-title":"Ital J Gastroenterol"},{"key":"e_1_2_5_32_2","first-page":"2723","article-title":"Liver\u2010protective action of silymarin therapy in chronic alcoholic liver diseases","volume":"130","author":"Feher J","year":"1989","journal-title":"Orv Hetil"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80285-7"},{"key":"e_1_2_5_34_2","first-page":"311","article-title":"Use of the Romanian product Silimarina in the treatment of chronic liver diseases","volume":"26","author":"Tanasescu C","year":"1988","journal-title":"Med Interne"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2004.06.015"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(89)90083-4"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.5414\/CPP40002"},{"issue":"1","key":"e_1_2_5_38_2","first-page":"PIII","article-title":"Single dose escalation phase I study to evaluate the pharmacokinetics (PK) of silymarin (Legalon\u00ae) and the effect of food in patients with chronic hepatitis C (HCV)","volume":"83","author":"Soule TA","year":"2008","journal-title":"Clin Pharmacol Expt Ther"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1556\/OH.2009.28517"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2003.12.002"},{"key":"e_1_2_5_41_2","doi-asserted-by":"publisher","DOI":"10.5414\/CPP41593"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.03.059"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F0091270009347475","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0091270009347475","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T20:58:02Z","timestamp":1739393882000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/0091270009347475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,4]]}},"alternative-id":["10.1177\/0091270009347475"],"URL":"https:\/\/doi.org\/10.1177\/0091270009347475","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4]]}}}