Tags

Type your tag names separated by a space and hit enter

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 2008; 36(9):1909-16DM

Abstract

Silymarin, used by 30 to 40% of liver disease patients, is composed of six major flavonolignans, each of which may contribute to silymarin's hepatoprotective properties. Previous studies have only described the pharmacokinetics for two flavonolignans, silybin A and silybin B, in healthy volunteers. The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients. Healthy volunteers and three patient cohorts were administered a single, 600-mg p.o. dose of milk thistle extract, and 14 blood samples were obtained over 24 h. Silybin A and B accounted for 43% of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38% in liver disease cohorts as a result of accumulation of silychristin (20-36%). Area under the curve (AUC(0-24h)) for the sum of total silymarin flavonolignans was 2.4-, 3.3-, and 4.7-fold higher for hepatitis C virus (HCV) noncirrhosis, nonalcoholic fatty liver disease (p <or= 0.03), and HCV cirrhosis cohorts (p <or= 0.03), respectively, compared with healthy volunteers (AUC(0-24h) = 2021 ng . h/ml). Caspase-3/7 activity correlated with the AUC(0-24h) for the sum of all silymarin conjugates among all subjects (R(2) = 0.52) and was 5-fold higher in the HCV cirrhosis cohort (p <or= 0.005 versus healthy). No correlation was observed with other measures of disease activity, including plasma alanine aminotransferase, interleukin 6, and 8-isoprostane F(2alpha), a measure of oxidative stress. These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease. Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans.

Authors+Show Affiliations

Division of Pharmacotherapy and Experimental Therapeutics,School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18566043

Citation

Schrieber, Sarah J., et al. "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 Metabolism and Disposition: the Biological Fate of Chemicals, vol. 36, no. 9, 2008, pp. 1909-16.
Schrieber SJ, Wen Z, Vourvahis M, et al. 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. 2008;36(9):1909-16.
Schrieber, S. J., Wen, Z., Vourvahis, M., Smith, P. C., Fried, M. W., Kashuba, A. D., & Hawke, R. L. (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 Metabolism and Disposition: the Biological Fate of Chemicals, 36(9), pp. 1909-16. doi:10.1124/dmd.107.019604.
Schrieber SJ, et al. 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. 2008;36(9):1909-16. PubMed PMID: 18566043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Schrieber,Sarah J, AU - Wen,Zhiming, AU - Vourvahis,Manoli, AU - Smith,Philip C, AU - Fried,Michael W, AU - Kashuba,Angela D M, AU - Hawke,Roy L, Y1 - 2008/06/19/ PY - 2008/6/21/pubmed PY - 2008/11/8/medline PY - 2008/6/21/entrez SP - 1909 EP - 16 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 36 IS - 9 N2 - Silymarin, used by 30 to 40% of liver disease patients, is composed of six major flavonolignans, each of which may contribute to silymarin's hepatoprotective properties. Previous studies have only described the pharmacokinetics for two flavonolignans, silybin A and silybin B, in healthy volunteers. The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients. Healthy volunteers and three patient cohorts were administered a single, 600-mg p.o. dose of milk thistle extract, and 14 blood samples were obtained over 24 h. Silybin A and B accounted for 43% of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38% in liver disease cohorts as a result of accumulation of silychristin (20-36%). Area under the curve (AUC(0-24h)) for the sum of total silymarin flavonolignans was 2.4-, 3.3-, and 4.7-fold higher for hepatitis C virus (HCV) noncirrhosis, nonalcoholic fatty liver disease (p <or= 0.03), and HCV cirrhosis cohorts (p <or= 0.03), respectively, compared with healthy volunteers (AUC(0-24h) = 2021 ng . h/ml). Caspase-3/7 activity correlated with the AUC(0-24h) for the sum of all silymarin conjugates among all subjects (R(2) = 0.52) and was 5-fold higher in the HCV cirrhosis cohort (p <or= 0.005 versus healthy). No correlation was observed with other measures of disease activity, including plasma alanine aminotransferase, interleukin 6, and 8-isoprostane F(2alpha), a measure of oxidative stress. These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease. Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans. SN - 1521-009X UR - https://www.unboundmedicine.com/medline/citation/18566043/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_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=18566043 DB - PRIME DP - Unbound Medicine ER -