title: Effect of continuous silymarin administration on oral talinolol pharmacokinetics in healthy volunteers.
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 (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.
authors: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors: Y
authors: Y
authors: Han
authors: D
authors: D
authors: Guo
authors: Y
authors: Y
authors: Chen
authors: Z-R
authors: ZR
authors: Tan
authors: H-H
authors: HH
authors: Zhou
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D011110:Polymorphism, Genetic; D011412:Propanolamines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012838:Silymarin / Q000008:administration & dosage* / Q000097:blood; D016037:Single-Blind Method
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D012838:Silymarin; C011550:talinolol