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Xenobiotica
the fate of foreign compounds in biological systems
Volume 39, 2009 - Issue 9
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Research Article

Effect of continuous silymarin administration on oral talinolol pharmacokinetics in healthy volunteers

, , , &
Pages 694-699 | Received 02 Apr 2009, Accepted 22 May 2009, Published online: 26 Jun 2009
 

Abstract

  1. The objective of this study was to investigate the effect of concomitantly administered silymarin on the pharmacokinetics of talinolol, a typical substrate for P-glycoprotein (P-gp), in healthy Chinese volunteers and its association with a multidrug resistance 1 (MDR1) C3435T genetic polymorphism.

  2. Eighteen healthy adult men (six MDR1 3435CC homozygotes, six MDR1 3435CT heterozygotes and six MDR1 3435TT homozygotes) were recruited in a two-phase, randomized, single-blind, crossover design. The pharmacokinetics of talinolol were measured after co-administration of placebo or 140 mg silymarin capsules three times daily for 14 days. Concentrations of talinolol in plasma were measured for up to 36 h after drug administration by liquid chromatography-mass spectrometry (HPLC-MS).

  3. The peak plasma concentration (Cmax) of talinolol was significantly higher after silymarin administration as compared with placebo (p = 0.007). The area under the plasma concentration–time curve from zero to 36 h (AUC0–36) and AUC0–∞ of talinolol was increased by 36.2% ± 33.2% and 36.5% ± 37.9%, respectively, by silymarin co-administration. The oral clearance (CL/F) of talinolol was decreased by 23.1% ± 16.6% (p < 0.001) during the silymarin-treated phase. No change in the time to peak concentration (tmax) and the blood elimination half-life (t1/2) of talinolol was observed between the placebo- and silymarin-treated phases.

  4. Co-administration of silymarin significantly increased the plasma concentration of talinolol in healthy volunteers.

Acknowledgements

The study was supported by a grant from Madaus AG, Cologne, Germany.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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