TY - JOUR T1 - Differences in the Disposition of Silymarin Between Patients with Non-Alcoholic Fatty Liver Disease and Chronic Hepatitis C JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.111.040212 SP - dmd.111.040212 AU - Sarah J Schrieber AU - Roy L Hawke AU - Zhiming Wen AU - Philip C. Smith AU - Rajender Reddy AU - Abdus S Wahed AU - Steven H Belle AU - Nezam H Afdhal AU - Victor J Navarro AU - Catherine M Meyers AU - Edward Doo AU - Michael W Fried Y1 - 2011/08/24 UR - http://dmd.aspetjournals.org/content/early/2011/08/24/dmd.111.040212.abstract N2 - Silymarin, derived from the milk thistle plant Silybum marianum and widely used for self-treatment of liver diseases, is comprised 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 if silymarin's disposition, and therefore its potential efficacy, varies between liver disease populations. Cohorts of eight subjects with non-cirrhotic liver disease were randomized 3:1 to oral silymarin or placebo (280 or 560 mg) every 8 hours for 7 days. 48-Hour blood sampling was conducted following the first and final doses. In general, plasma concentrations of silybin A and silybin B were higher while concentrations of conjugates were lower in NAFLD compared to HCV. After adjusting AUC0-8h for weight and dose, only silybin B and silybin B conjugates differed significantly between disease types. For NAFLD, the adjusted mean AUC0-8h was higher for silybin B (p<0.05) but lower for silybin B conjugates (p<0.05) compared to HCV. At the 280 mg dose, steady-state plasma concentrations of silybin B conjugates for NAFLD subjects were characterized by 46% lower AUC0-8h(p<0.05) and 42% lower Cmax (p<0.05) compared to HCV subjects. Evidence of enterohepatic cycling of flavonolignans was only observed in NAFLD subjects. In summary, silymarin's efficacy may be more readily observed in NAFLD patients due to higher flavonolignan plasma concentrations and more extensive enterohepatic cycling compared to patients with HCV. ER -