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

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 (C-max) 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 (AUC(0-36)) and AUC(0-infinity) 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 (t(max)) and the blood elimination half-life (t(1/2)) 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.