Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
Eur J Clin Pharmacol. 2010 May;66(5):497-502. doi: 10.1007/s00228-010-0796-3. Epub 2010 Feb 24.
This study aimed to investigate the effect of rifampicin, an inducer of CYP3A4 and P-glycoprotein, on the pharmacokinetics and pharmacodynamics of aliskiren, a renin inhibitor used in the treatment of hypertension.
In a randomized crossover study, 12 healthy volunteers took 600 mg rifampicin or placebo once daily for 5 days. On day 6, they ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h and urine concentrations up to 12 h; pharmacodynamic variables were measured up to 24 h.
Rifampicin reduced the peak plasma aliskiren concentration (C(max)) by 39% (95% confidence interval 0.41, 0.90; P = 0.017) and the area under the plasma aliskiren concentration-time curve AUC(0-infinity) by 56% (95% confidence interval 0.35, 0.56; P < 0.001). Rifampicin had no significant effect on aliskiren elimination half-life (t(1/2)) or its renal clearance (Cl(renal)). Plasma renin activity 24 h after aliskiren intake was 61% higher during the rifampicin phase than during the placebo phase (P = 0.008).
Rifampicin considerably reduces the plasma concentrations and the renin-inhibiting effect of aliskiren by decreasing its oral bioavailability.
本研究旨在探讨利福平（一种 CYP3A4 和 P-糖蛋白诱导剂）对肾素抑制剂阿利克仑（用于治疗高血压）的药代动力学和药效学的影响。
在一项随机交叉研究中，12 名健康志愿者每日服用利福平 600mg 或安慰剂，共 5 天。第 6 天，单次服用 150mg 阿利克仑。测量至 72 小时的血浆阿利克仑浓度和至 12 小时的尿液浓度；测量至 24 小时的药效学变量。
利福平使阿利克仑的峰血浆浓度（C(max)）降低 39%（95%置信区间 0.41，0.90；P = 0.017），使 AUC(0-∞)降低 56%（95%置信区间 0.35，0.56；P < 0.001）。利福平对阿利克仑消除半衰期（t(1/2)）或肾清除率（Cl(renal)）没有显著影响。阿利克仑摄入后 24 小时的血浆肾素活性在利福平阶段比安慰剂阶段高 61%（P = 0.008）。
利福平通过降低其口服生物利用度，显著降低阿利克仑的血浆浓度和抑制肾素的作用。
