Clinical Pharmacy & Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Renmin Middle Road 139, Changsha, Hunan 410011, China.
Eur J Clin Pharmacol. 2013 Mar;69(3):515-21. doi: 10.1007/s00228-012-1391-6. Epub 2012 Sep 15.
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.
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.
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.
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.
研究重复甘草酸苷摄入对人体 P-糖蛋白（P-gp）活性探针药物他林洛尔口服药代动力学的影响。
本研究纳入 14 名健康成年男性志愿者，采用两周期随机交叉设计。每个周期志愿者连续 6 天接受安慰剂或复方甘草酸苷片（甘草酸苷 75mg，每日 3 次）治疗，第 7 天给予单剂量 100mg 他林洛尔，通过高效液相色谱法（紫外检测器）测定血浆中他林洛尔浓度，采用非房室模型分析方法对他林洛尔的血药浓度-时间曲线进行描述。使用 DAS ver. 2.1 软件计算他林洛尔的药代动力学参数，采用 SPSS ver. 13.0 软件进行统计分析。采用方差分析比较两种处理方法的药代动力学参数均值，以 P＜0.05 为差异有统计学意义。
研究期间所有治疗均耐受良好。甘草酸苷和安慰剂组的他林洛尔 AUC（0-∞）几何均数±标准差分别为 2218.3±724.3ng·h/mL 和 1988.2±649.2ng·h/mL。甘草酸苷：安慰剂比值的调整几何均数（AUC（0-∞）和 C（max））90%置信区间完全在[80，125]范围内。连续 6 天甘草酸苷治疗未显著改变他林洛尔的药代动力学参数（AUC（0-∞）、AUC（0-24）、C（max）、t（max）、t（1/2））。
在本试验中，连续甘草酸苷给药对 P-gp 的表达没有诱导作用。需要进一步研究同时给予甘草酸苷和 P-gp 底物时甘草酸苷对 P-gp 功能的直接抑制作用。
