Premium
Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics of Ribavirin and Its Major Metabolite in Rats
Author(s) -
Liao Sha,
Jin Xueyuan,
Li Jinglai,
Zhang Tianhong,
Zhang Wenpeng,
Shi Weiguo,
Fan Shiyong,
Wang Xiaoying,
Wang Juan,
Zhong Bohua,
Zhang Zhenqing
Publication year - 2016
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5567
Subject(s) - glycyrrhizin , oxymatrine , pharmacokinetics , ribavirin , pharmacology , metabolite , medicine , pharmacognosy , traditional medicine , active metabolite , chemistry , virology , biological activity , in vitro , biochemistry , virus , hepatitis c virus
The herb‐derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral ( PO ) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, PO ), glycyrrhizin (15 mg/kg, intraperitoneal [ IP ]), or oxymatrine (60 mg/kg, PO ). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration‐time curve (AUC 0–t ) and the peak plasma concentration (C max ) of ribavirin and ribavirin base by 31.2–44.5% and 48.9–50.0%, respectively. Glycyrrhizin significantly decreased the C max and AUC 0–t of both ribavirin and its metabolite by 35.3–37.6% and 38.6–39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and C max . Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the C max (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine. Copyright © 2016 John Wiley & Sons, Ltd.