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

Abstract

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.

Altered Drug Metabolism and Transport in Pathophysiological Conditions

“…However, plasma levels of APAP-G were also elevated in MCD rats, similar to that observed in children (Barshop et al, 2011). A clinical study evaluated the effect of NAFLD on PK of silymarin (Schrieber et al, 2008). The AUC 0-24h for the sum of total silymarin flavonolignans was ~3-4 fold higher in patients with NAFLD (p<0.03), compared with healthy volunteers.…”

Antiviral effects of silymarin against hepatitis C

“…[6][7][8][9][10] The first pharmacokinetic evaluation of SM in patients with liver disease recently indicated there may be substantial differences in silymarin metabolism between patients with mild and advanced chronic HCV, resulting in three-fold to five-fold higher plasma concentrations of flavonolignan conjugates as compared to healthy subjects. 11 Still, concentrations of SM required to inhibit HCV replication in vitro appear to be one to two orders of magnitude higher than those observed in patients with chronic HCV using customary doses.…”

“…Moreover, trials that only dosed SM one to two times per day may not have achieved high enough plasma concentrations due to the rapid half-life observed in patients with liver disease. 11 Therefore, if SM exerts any antiviral activity in vivo, it may be transient, and would require adequate plasma and, perhaps more importantly, liver concentrations following repeated daily dosing.…”

Limited Sampling Estimates of Epigallocatechin Gallate Exposures in Cirrhotic and Noncirrhotic Patients With Hepatitis C After Single Oral Doses of Green Tea Extract

“…Differences in the disposition of silymarin, another herbal product used by patients for the self-treatment of liver disease, has been seen in liver disease. 17,18 Alterations in the expression of hepatobiliary transporters induced by liver disease, which may lead to differences in drug disposition, have been reported. 19 The risk of hepatic decompensation as a result of drug induced liver injury is greatest in patients with cirrhosis and increases with disease progression defined by Child Pugh classification .…”