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Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C
- Source :
- The Journal of Clinical Pharmacology. 50:434-449
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Silymarin, derived from the milk thistle plant Silybum marianum, is widely used for self-treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose-exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well-compensated, chronic noncirrhotic HCV who failed interferon-based therapy were randomized 3:1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg silymarin were administered every 8 hours for 7 days. Steady-state exposures for silybin A and silybin B increased 11-fold and 38-fold, respectively, with a 5-fold increase in dose, suggesting nonlinear pharmacokinetics. No drug-related adverse events were reported, and no clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.
- Subjects :
- Adult
Liver Cirrhosis
Male
Hepacivirus
Hepatitis C virus
Administration, Oral
Pharmacology
medicine.disease_cause
Placebo
Article
Silybum marianum
Cohort Studies
Double-Blind Method
Pharmacokinetics
medicine
Humans
Pharmacology (medical)
Adverse effect
Dose-Response Relationship, Drug
biology
Milk Thistle
business.industry
Hepatitis C
Hepatitis C, Chronic
Middle Aged
medicine.disease
biology.organism_classification
RNA, Viral
Female
business
Silymarin
Subjects
Details
- ISSN :
- 00912700
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Pharmacology
- Accession number :
- edsair.doi.dedup.....730ff309c165ac05eac1020d50229fe0