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.