Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: Comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxiin pharmacokinetics
Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: Comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxiin pharmacokinetics
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DOI：
10.1002/mnfr.200700081
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发表时间：
2008-06-01
影响因子：
5.2
通讯作者：
Battu, Sunil K.
中科院分区：
文献类型：
--
作者：
Gurley, Bill J.;Swain, Ashley;Battu, Sunil K.
植物补充剂与P-糖蛋白（P-gp）底物药物同时给药可能会产生临床显著的草药-药物相互作用。本研究评价了圣约翰草和紫锥菊对地高辛（一种公认的P-gp底物）药代动力学的影响。18名健康志愿者被随机分配接受标准化的圣约翰草（300毫克，每日三次）或紫锥菊（267毫克，每日三次）补充14天，随后是30天的洗脱期。受试者还随机接受利福平（300 mg，每日两次，7天）和克拉霉素（500 mg，每日两次，7天），分别作为P-gp诱导和抑制的阳性对照。在每次补充和对照期之前和之后口服地高辛（Lanoxin（R）0.25 mg）。在24小时内获得连续的地高辛血浆浓度，并通过化学发光免疫测定法进行分析。比较曲线下面积（AUC）（（0-3））、AUC（（0-24））、消除半衰期和最大血清浓度，以评估圣约翰草、紫锥菊、利福平和克拉霉素对地高辛处置的影响。圣约翰草和利福平均使AUC（（0-3））、AUC（（0-24））显著降低（p < 0.05）。而克拉霉素则显著增加上述指标（p < 0.05）。补充紫锥菊不影响地高辛的药代动力学。具有临床意义的P-gp介导的草药-药物相互作用更可能发生在圣约翰草中，而不是紫锥菊中。
Concomitant administration of botanical supplements with drugs that are P-glycoprotein (P-gp) substrates may produce clinically significant herb-drug interactions. This study evaluated the effects of St. John's wort and Echinacea on the pharmacokinetics of digoxin, a recognized P-gp substrate. Eighteen healthy volunteers were randomly assigned to receive a standardized St. John's wort (300 mg three times daily) or Echinacea (267 mg three times daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (300 mg twice daily, 7 days) and clarithromycin (500 mg twice daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin (R) 0.25 mg) was administered orally before and after each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), elimination half-life, and maximum serum concentration were used to assess the effects of St. John's wort, Echinacea, rifampin, and clarithromycin on digoxin disposition. St. John's wort and rifampin both produced significant reductions (p < 0.05) in AUC((0-3)), AUC((0-24)). and C-max, while clarithromycin increased these parameters significantly (p < 0.05). Echinacea supplementation did not affect digoxin pharmacokinetics. Clinically significant P-gp-mediated herb-drug interactions are more likely to occur with St. John's wort than with Echinacea.