Planta Med 2007; 73(14): 1429-1435
DOI: 10.1055/s-2007-990256
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of Silymarin on Oral Nifedipine Pharmacokinetics

Uwe Fuhr1 , Svane Beckmann-Knopp1 , Alexander Jetter1 , 4 , Hendrik Lück2 , Ulrich Mengs3
  • 1Department of Pharmacology, University Hospital, University of Cologne, Cologne, Germany
  • 2ITECRA Institute for Tailored Early Clinical Research and Advice GmbH & Co. KG, Cologne, Germany;
  • 3Madaus GmbH, Cologne, Germany
  • 4Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital Zurich, Zürich, Switzerland
Further Information

Publication History

Received: May 29, 2007 Revised: September 24, 2007

Accepted: October 2, 2007

Publication Date:
30 October 2007 (online)

Abstract

Silibinin, the main component of silymarin (a milk thistle extract used for treatment of liver injury), has been shown to inhibit CYP3A4 in human liver microsomes. The present study was conducted to examine whether inhibition of CYP3A4 by silymarin is also present in vivo. Immediate release nifedipine (10 mg) was administered as a CYP3A4 test drug either alone or with co-administration of silymarin (280 mg administered 10 hours and 1.5 hours prior to the administration of nifedipine) to 16 healthy male volunteers (mean age 27 years, mean body weight 77 kg). Nifedipine and silibinin concentrations were quantified by HPLC, heart rate and blood pressure were monitored for safety reasons. Pharmacokinetic parameters were calculated by non-compartmental methods, and the potential interaction by silymarin was handled as an equivalence problem. We found that nifedipine AUC was 1.13-fold higher (90 % CI, 0.97- to 1.32-fold) in the silymarin period, Cmax values were 0.70-fold (90 % CI, 0.39- to 1.27-fold) of those of the reference period, with a trend to delayed absorption in the silymarin period. Intraindividual variability especially for Cmax (intrasubject CV 120 %) was unexpectedly high. There was no meaningful effect on hemodynamic parameters. In conclusion, our data suggest that co-administration of silymarin does not considerably change the extent of absorption or metabolism of nifedipine but may decrease the absorption rate. Silymarin thus is not a potent CYP3A4 inhibitor in vivo.

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Prof. Dr. Uwe Fuhr

Department of Pharmacology

Clinical Pharmacology

University of Cologne

Gleueler Straße 24

50931 Cologne

Germany

Phone: +49-221-478-5230

Fax: +49-221-478-7011

Email: uwe.fuhr@uk-koeln.de