The Pregnane X Receptor Agonist St John's Wort Has No Effects on the Pharmacokinetics and Pharmacodynamics of Repaglinide
The Pregnane X Receptor Agonist St John's Wort Has No Effects on the Pharmacokinetics and Pharmacodynamics of Repaglinide
复制标题
孕烷X受体激动剂圣约翰草对瑞格列奈的药代动力学和药效学没有影响
DOI：
10.2165/11587310-000000000-00000
复制
发表时间：
2011-01-01
影响因子：
4.5
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Fan, Lan;Zhou, Gan;Zhang, Wei
背景和目的：圣约翰草（SJW；贯叶连翘）是治疗情绪障碍最常用的草药之一。本研究旨在探讨妊娠X受体（PXR）激动剂SJW对广泛使用的降糖药物瑞格列奈的药代动力学和药效学影响。方法：在一项两期随机交叉研究中，15名具有特定溶质载体有机阴离子转运体家族成员1B1 （SLCO1B1）基因型的健康受试者，每天3次给予SJW 325 mg或安慰剂预处理，连续14天，在给予瑞格列奈15分钟后给予单剂量瑞格列奈1 mg，随后给予75g葡萄糖。结果：在所有受试者中，SJW对血药浓度-时间曲线下从时间0到无穷远的总面积（AUC（无穷远））、血药浓度峰值（C-max）和瑞格列奈消除半衰期（t(1/2)）均无影响。此外，SJW对瑞格列奈的降糖和胰岛素升高作用无显著影响。结论：服用SJW 14 d对瑞格列奈的药代动力学和药效学无显著影响。
Background and Objectives: St John's wort (SJW; Hypericum perforatum) has been one of the most commonly used herbal remedies for mood disorders. This study aimed to investigate the effect of SJW, a pregnane X receptor (PXR) agonist, on the pharmacokinetics and pharmacodynamics of repaglinide, a widely consumed glucose-lowering drug.Methods: In a two-phase, randomized, crossover study with a 4-week washout period between phases, 15 healthy subjects with specific solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes were given pretreatment with SJW 325 mg or placebo three times daily for 14 days, and a single dose of repaglinide 1 mg was administered followed by 75g glucose at 15 minutes after repaglinide administration.Results: In all subjects, SJW had no effect on the total area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)), the peak plasma concentration (C-max) or the elimination half-life (t(1/2)) of repaglinide. In addition, SJW had no significant effect on the blood glucose-lowering and insulin-elevating effects of repaglinide.Conclusion: Consumption of SJW for 14 days had no clinically significant effect on the pharmacokinetics and pharmacodynamics of repaglinide.