Silymarin and trazodone interactions.
Article Type: Report
Subject: Bioflavonoids (Physiological aspects)
Bioflavonoids (Research)
Flavones (Physiological aspects)
Flavones (Research)
Flavonoids (Physiological aspects)
Flavonoids (Research)
Drug interactions (Research)
Milk thistle (Physiological aspects)
Milk thistle (Research)
Trazodone (Dosage and administration)
Trazodone (Physiological aspects)
Trazodone (Research)
Author: Finney-Brown, Tessa
Pub Date: 12/22/2009
Publication: Name: Australian Journal of Medical Herbalism Publisher: National Herbalists Association of Australia Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 National Herbalists Association of Australia ISSN: 1033-8330
Issue: Date: Winter, 2009 Source Volume: 21 Source Issue: 4
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: Australia Geographic Code: 8AUST Australia
Accession Number: 215249522
Full Text: Chang J, Wu Y, Lee W, Lin L, Tsai T. 2009. Herb drug interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats. Chemico-Biol Interactions. In print.

St Mary's thistle, Silybum marianum, is one of the most commonly used botanical agents, beneficial due to its hepatoprotective, hepatotrophorestorative, antioxidant and anti-inflammatory properties. Its key active component is silymarin, composed of a number of polyphenolic flavonoids including silybin, isosilybin and silidianin.

As silymarin is currently undergoing clinical trials as treatment for hepatitis C, and antidepressants are a commonly prescribed agent in those with the condition, the authors of this study set out to investigate the interaction between the herbal component and these drugs. Trazodone hydrochloride is a second generation antidepressant agent which is metabolised by the cytochrome P450 enzymes CYP3A4 and CYP1A2. Affecting these enzymes may alter the metabolism and activity of the drug.

Previous studies have shown that silymarin has the ability to inhibit the activity of CYP3A4 in a single dose and induce intestinal P-glycoprotein and CYP3A4 with repeated administrations. An in vivo investigation was carried out on a number of male Sprague-Dawley rats. They were randomly divided into six groups in a parallel study design where one group was treated concomitantly with silymarin (1.0 g/kg) 4 hr prior to trazodone (5 mg/ kg) administration; a control group was treated with vehicle for seven consecutive days then trazodone (5 mg/ kg) was given on the 8th day; two groups were pretreated with 0.175 and 0.35 g/kg silibin for seven consecutive days then trazodone (5 mg/kg) was given on the 8th day; and two groups treated with 0.5 and 1.0 g/kg of silymarin for seven consecutive days then trazodone (5 mg/kg) was given on the 8th day.

All rats were then anesthetised and continuous microdialysis sampling took blood and bile for analysis by HPLC-fluorescence detection of trazadone concentration.

The authors note that it was inevitable that the surgical procedures performed on the rats and the concurrent anesthesia may affect the pharmacokinetics of the antidepressant, which was why a control group was included in the study.

From the results it seemed that concurrent silymarin administration (four hours earlier) reduced the biliary excretion of trazodone. In the repeated administration groups the area under the concentration time curve (AUC, a pharmacokinetic parameter) of bile and the AUC bile/ AUC blood ratio increased, but only the AUC of bile showed significant differences that were dose dependant. The silymarin pretreatments showed more obvious effect than the silybin treatments.

Only high repeated doses of silymarin (1.0 g/kg) significantly affected the pharmacokinetics of trazadone, increasing the clearance of the drug. The authors note that this is quite a high amount of silymarin to ingest and that at the administration of normal daily doses there would be no marked effect expected upon the metabolism of trazodone. Thus it should be safe to take the two concomitantly in normal doses.

Tessa Finney-Brown MNHAA
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