title: Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics of Ribavirin and Its Major Metabolite in Rats.
abstract: 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 (p.o.) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, p.o.), glycyrrhizin (15 mg/kg, intraperitoneal [i.p.]), or oxymatrine (60 mg/kg, p.o.). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration-time curve (AUC0-t ) and the peak plasma concentration (Cmax ) of ribavirin and ribavirin base by 31.2-44.5% and 48.9-50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0-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 Cmax . Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (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.
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liao
authors.affiliation: The International Therapy Center for Liver Disease, Military 302 Hospital, Beijing, 100039, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Jinglai
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Bohua
authors.initials: B
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D004347:Drug Interactions; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D008297:Male; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D019695:Glycyrrhizic Acid; D011807:Quinolizines; D012254:Ribavirin; D012838:Silymarin; C037573:oxymatrine; D000093842:Matrines
keywords: drug-drug interaction; glycyrrhizin; oxymatrine; pharmacokinetics; ribavirin; silymarin