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Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C.
Drug Metab Dispos. 2011 Dec; 39(12):2182-90.DM

Abstract

Silymarin, derived from the milk thistle plant Silybum marianum and widely used for self-treatment of liver diseases, is composed of six major flavonolignans including silybin A and silybin B, which are the predominant flavonolignans quantified in human plasma. The single- and multiple-dose pharmacokinetics of silymarin flavonolignans were examined in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV) to determine whether the disposition of silymarin and therefore its potential efficacy vary among liver disease populations. Cohorts of eight subjects with noncirrhotic liver disease were randomized 3:1 to oral silymarin or placebo (280 or 560 mg) every 8 h for 7 days. Forty-eight-hour blood sampling was conducted after the first and final doses. In general, plasma concentrations of silybin A and silybin B were higher, whereas concentrations of conjugates were lower in NAFLD compared with HCV. After adjustment of the area under plasma concentration-time curve from 0 to 8 h (AUC(0-8 h)) for weight and dose, only silybin B and silybin B conjugates differed significantly between disease types. For NAFLD, the adjusted mean AUC(0-8 h) was higher for silybin B (p < 0.05) but lower for silybin B conjugates (p < 0.05) compared with that for HCV. At the 280-mg dose, steady-state plasma concentrations of silybin B conjugates for NAFLD subjects were characterized by 46% lower AUC(0-8 h) (p < 0.05) and 42% lower C(max) (p < 0.05) compared with HCV subjects. Evidence of enterohepatic cycling of flavonolignans was only observed in NAFLD subjects. In summary, the efficacy of silymarin may be more readily observed in NAFLD patients because of their higher flavonolignan plasma concentrations and more extensive enterohepatic cycling compared with those in HCV patients.

Authors+Show Affiliations

Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, NC 27599-7360, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21865319

Citation

Schrieber, Sarah J., et al. "Differences in the Disposition of Silymarin Between Patients With Nonalcoholic Fatty Liver Disease and Chronic Hepatitis C." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 39, no. 12, 2011, pp. 2182-90.
Schrieber SJ, Hawke RL, Wen Z, et al. Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C. Drug Metab Dispos. 2011;39(12):2182-90.
Schrieber, S. J., Hawke, R. L., Wen, Z., Smith, P. C., Reddy, K. R., Wahed, A. S., Belle, S. H., Afdhal, N. H., Navarro, V. J., Meyers, C. M., Doo, E., & Fried, M. W. (2011). Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 39(12), 2182-90. https://doi.org/10.1124/dmd.111.040212
Schrieber SJ, et al. Differences in the Disposition of Silymarin Between Patients With Nonalcoholic Fatty Liver Disease and Chronic Hepatitis C. Drug Metab Dispos. 2011;39(12):2182-90. PubMed PMID: 21865319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C. AU - Schrieber,Sarah J, AU - Hawke,Roy L, AU - Wen,Zhiming, AU - Smith,Philip C, AU - Reddy,K Rajender, AU - Wahed,Abdus S, AU - Belle,Steven H, AU - Afdhal,Nezam H, AU - Navarro,Victor J, AU - Meyers,Catherine M, AU - Doo,Edward, AU - Fried,Michael W, Y1 - 2011/08/24/ PY - 2011/8/26/entrez PY - 2011/8/26/pubmed PY - 2012/4/10/medline SP - 2182 EP - 90 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 39 IS - 12 N2 - Silymarin, derived from the milk thistle plant Silybum marianum and widely used for self-treatment of liver diseases, is composed of six major flavonolignans including silybin A and silybin B, which are the predominant flavonolignans quantified in human plasma. The single- and multiple-dose pharmacokinetics of silymarin flavonolignans were examined in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis C virus (HCV) to determine whether the disposition of silymarin and therefore its potential efficacy vary among liver disease populations. Cohorts of eight subjects with noncirrhotic liver disease were randomized 3:1 to oral silymarin or placebo (280 or 560 mg) every 8 h for 7 days. Forty-eight-hour blood sampling was conducted after the first and final doses. In general, plasma concentrations of silybin A and silybin B were higher, whereas concentrations of conjugates were lower in NAFLD compared with HCV. After adjustment of the area under plasma concentration-time curve from 0 to 8 h (AUC(0-8 h)) for weight and dose, only silybin B and silybin B conjugates differed significantly between disease types. For NAFLD, the adjusted mean AUC(0-8 h) was higher for silybin B (p < 0.05) but lower for silybin B conjugates (p < 0.05) compared with that for HCV. At the 280-mg dose, steady-state plasma concentrations of silybin B conjugates for NAFLD subjects were characterized by 46% lower AUC(0-8 h) (p < 0.05) and 42% lower C(max) (p < 0.05) compared with HCV subjects. Evidence of enterohepatic cycling of flavonolignans was only observed in NAFLD subjects. In summary, the efficacy of silymarin may be more readily observed in NAFLD patients because of their higher flavonolignan plasma concentrations and more extensive enterohepatic cycling compared with those in HCV patients. SN - 1521-009X UR - https://www.unboundmedicine.com/medline/citation/21865319/Differences_in_the_disposition_of_silymarin_between_patients_with_nonalcoholic_fatty_liver_disease_and_chronic_hepatitis_C_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=21865319 DB - PRIME DP - Unbound Medicine ER -