Wang Zaiqi, Hamman Mitchell A, Huang Shiew-Mei, Lesko Lawrence J, Hall Stephen D
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Clin Pharmacol Ther. 2002 Jun;71(6):414-20. doi: 10.1067/mcp.2002.124080.
St John's wort is a popular over-the-counter dietary supplement and herbal remedy that has been implicated in drug interactions with several substrates of P-glycoprotein. The effect of St John's wort on P-glycoprotein activity in vivo was examined with use of fexofenadine as selective probe drug.
A 3-period, open-label, fixed-schedule study design was used. Fexofenadine, 60 mg, was administered orally before administration of St John's wort, with a single dose of St John's wort (900 mg), and after 2 weeks of treatment with St John's wort (300 mg 3 times a day) to determine P-glycoprotein activity.
A single dose of St John's wort significantly (P <.05) increased the maximum plasma concentration of fexofenadine by 45% and significantly (P <.05) decreased the oral clearance by 20%, with no change in half-life or renal clearance. Long-term administration of St John's wort did not cause a significant change in fexofenadine disposition relative to the untreated phase. Compared with the single-dose treatment phase, long-term St John's wort caused a significant 35% decrease (P <.05) in maximum plasma concentration and a significant 47% increase (P <.05) in fexofenadine oral clearance.
A single dose of St John's wort resulted in a significant inhibition of intestinal P-glycoprotein. Long-term treatment with St John's wort reversed the changes in fexofenadine disposition observed with single-dose administration.
圣约翰草是一种广受欢迎的非处方膳食补充剂和草药疗法，已被证明与几种P-糖蛋白底物存在药物相互作用。本研究以非索非那定作为选择性探针药物，检测圣约翰草对体内P-糖蛋白活性的影响。
采用三阶段、开放标签、固定时间表的研究设计。在服用圣约翰草之前口服60 mg非索非那定，然后服用单剂量圣约翰草（900 mg），并在服用圣约翰草（300 mg，每日3次）2周后测定P-糖蛋白活性。
单剂量圣约翰草显著（P <.05）使非索非那定的最大血浆浓度增加45%，并显著（P <.05）使口服清除率降低20%，半衰期和肾脏清除率无变化。与未治疗阶段相比，长期服用圣约翰草并未导致非索非那定处置发生显著变化。与单剂量治疗阶段相比，长期服用圣约翰草使最大血浆浓度显著降低35%（P <.05），非索非那定口服清除率显著增加47%（P <.05）。
单剂量圣约翰草可显著抑制肠道P-糖蛋白。长期服用圣约翰草可逆转单剂量给药时观察到的非索非那定处置变化。
