title: Lack of effect of continuous glycyrrhizin administration on the pharmacokinetics of the P-glycoprotein substrate talinolol in healthy volunteers.
abstract: OBJECTIVE
  To investigate the effects of repeated glycyrrhizin ingestion on the oral pharmacokinetics of talinolol, a probe drug for P-glycoprotein (P-gp) activity in humans.
  
  
  METHODS
  Fourteen healthy adult male subjects were enrolled in a two-phase randomized crossover-design study. In each phase the volunteers received placebo or compound glycyrrhizin tablets (75 mg glycyrrhizin three times daily) for 6 days. On the seventh day, a single oral dose of 100 mg talinolol was administered, and blood samples were obtained to determine plasma talinolol concentrations, measured in plasma by high-performance liquid chromatography with an ultraviolet detector. Non-compartmental analysis was used to characterize talinolol plasma concentration-time profiles. All pharmacokinetics parameters were calculated using DAS ver. 2.1 software, and statistical analyses were performed with SPSS ver. 13.0 software. Analysis of variance was used to check the difference of the means of the pharmacokinetic parameters between the two treatments at a significance level of 0.05.
  
  
  RESULTS
  All treatments were well tolerated during the study period. The geometric mean ± standard deviation of the AUC(0-∞) for talinolol treated by glycyrrhizin and talinolol treated by placebo was 2,218.3 ± 724.3 and 1,988.2 ± 649.2 ng·h/mL, respectively. The 90 % confidence intervals for the ratio of adjusted geometric means (glycyrrhizin:placebo) for AUC(0-∞) and C (max) fell wholly within the interval [80, 125]. Six days of glycyrrhizin treatment resulted in no significant alterations in the pharmacokinetic parameters (AUC(0-∞), AUC(0-24), C (max), t (max), t (½)) for talinolol.
  
  
  CONCLUSIONS
  Continuous glycyrrhizin administration had no induction effect on the expression of P-gp in our trial. Further research is needed to study the direct inhibition effect of glycyrrhizin on the function of P-gp with the simultaneous administration of both glycyrrhizin and P-gp substrate.
authors.affiliation: Clinical Pharmacy & Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Renmin Middle Road 139, Changsha, Hunan 410011, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yan
authors.forename: Ping-Fei
authors.initials: PF
authors.lastname: Fang
authors.forename: Huan-De
authors.initials: HD
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Cai
authors.forename: Qin-You
authors.initials: QY
authors.lastname: Tan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000284:Administration, Oral; D000704:Analysis of Variance; D019540:Area Under Curve; D002681:China; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D019695:Glycyrrhizic Acid / Q000008:administration & dosage*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012984:Software; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011412:Propanolamines; D013607:Tablets; C011550:talinolol; D019695:Glycyrrhizic Acid