Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects.
Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects.
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DOI：
10.1592/phco.30.8.797
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发表时间：
2010-08
期刊：
影响因子：
4.1
通讯作者：
Kovacs JA
中科院分区：
文献类型：
--
作者：
Penzak SR;Robertson SM;Hunt JD;Chairez C;Malati CY;Alfaro RM;Stevenson JM;Kovacs JA
分别使用探针底物咪达唑仑和非索非那定测定紫锥菊对洛匹那韦-利托那韦药代动力学以及对CYP 3A和P-糖蛋白（P-gp）活性的影响。开放标签、单序列药代动力学研究。联邦政府研究医院门诊部。13名（8名男性）健康志愿者（中位年龄：31岁）。健康志愿者接受洛匹那韦-利托那韦（400/100 mg），每日两次，持续30天。在研究第16天，受试者开始服用紫锥菊500 mg，每日三次，持续四周，前两周与洛匹那韦-利托那韦联合。在洛匹那韦-利托那韦给药的第15天和第30天（分别为紫锥菊给药前和给药后），在12小时内收集系列血液样品，以使用非房室方法测定洛匹那韦和利托那韦的浓度和随后的药代动力学参数。研究受试者还在紫锥菊治疗28天之前和之后接受咪达唑仑（8 mg口服）和非索非那定（120 mg口服）单次给药，以分别评估CYP 3A和P-糖蛋白（P-gp）活性。无论是洛匹那韦或利托那韦药代动力学显着改变2周的松果菊联合给药。洛匹那韦0 - 12小时药时曲线下面积（AUC 0 -12）和最大浓度（紫锥菊治疗后/治疗前）的几何均值比（GMR，90%CI）分别为0.96（0.83，1.10）和1.00（0.88，1.12）（P > 0.05）。相反，咪达唑仑从时间0至无穷大的AUC（AUC 0-∞）和口服清除率的GMR（90% CI）分别为0.73（0.61，0.85）（P = 0.008）和1.37（1.10，1.63）（P = 0.02）。非索非那定的药代动力学在紫锥菊给药前后无显著差异（P > 0.05）。紫锥菊诱导CYP 3A活性，但不改变洛匹那韦浓度，最有可能是由于存在强效CYP 3A抑制剂利托那韦。紫锥菊不太可能改变利托那韦增强蛋白酶抑制剂的药代动力学，但可能导致其他CYP 3A底物的血浆浓度适度降低。
To determine the influence of Echinacea purpurea on the pharmacokinetics of lopinavir-ritonavir, and on CYP3A and P-glycoprotein (P-gp) activity using the probe substrates midazolam, and fexofenadine, respectively. Open label, single-sequence pharmacokinetic study. Outpatient clinic in a Federal Government research hospital. Thirteen (8 males) healthy volunteers (median age: 31 yrs). Healthy volunteers received lopinavir-ritonavir (400/100 mg) twice daily for 30 days. On study day 16, subjects began taking Echinacea purpurea 500 mg three times daily, which they continued for four weeks, the first two weeks in combination with lopinavir-ritonavir. On days 15 and 30 of lopinavir-ritonavir administration (pre and post-Echinacea, respectively), serial blood samples were collected over 12 hrs to determine lopinavir and ritonavir concentrations and subsequent pharmacokinetic parameters using non-compartmental methods. Study subjects also received single doses of midazolam (8 mg orally) and fexofenadine (120 mg orally) before- and after 28 days of Echinacea purpurea to assess CYP3A and P-glycoprotein (P-gp) activity, respectively. Neither lopinavir nor ritonavir pharmacokinetics were significantly altered by 2 weeks of Echinacea coadministration. The geometric mean ratios (GMR, 90% CI) for lopinavir area under the concentration vs. time curve from zero to 12 hrs (AUC0–12) and maximum concentration (post-Echinacea/pre-Echinacea) were 0.96 (0.83, 1.10) and 1.00 (0.88, 1.12), respectively (P > 0.05). Conversely, GMRs (90% CIs) for midazolam AUC from time zero to infinity (AUC0-∞) and oral clearance were 0.73 (0.61, 0.85) (P = 0.008) and 1.37 (1.10, 1.63) (P = 0.02), respectively. Fexofenadine pharmacokinetics did not significantly differ pre- and post-echinacea administration (P > 0.05). Echinacea purpurea induced CYP3A activity but did not alter lopinavir concentrations, most likely due to the presence of the potent CYP3A inhibitor, ritonavir. Echinacea purpurea is unlikely to alter the pharmacokinetics of ritonavir-boosted protease inhibitors but may cause modest decreases in plasma concentrations of other CYP3A substrates.
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影响因子：
7.9
作者：
Budzinski, JW;Foster, BC;Arnason, JT
通讯作者：
Arnason, JT
影响因子：
168.9
作者：
Piscitelli, SC;Burstein, AH;Falloon, J
通讯作者：
Falloon, J
艾滋病毒感染者使用辅助和替代药物及替代常规疗法的情况
DOI：
10.1097/00126334-200306010-00007
发表时间：
2003-06-01
影响因子：
3.6
作者：
Hsiao, AF;Wong, MD;Wenger, NS
通讯作者：
Wenger, NS
DOI：
10.1111/j.1365-2710.2003.00542.x
发表时间：
2004-02-01
影响因子：
2
作者：
Goel, V;Lovlin, R;Basu, TK
通讯作者：
Basu, TK
影响因子：
4.9
作者：
Morse, GD;Rosenkranz, S;Reichman, RC
通讯作者：
Reichman, RC