临床aliskiren的药代学和药效学。
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Vaidyanathan年代,Jarugula V,兹•哈,霍华德D,多尔WP
临床aliskiren的药代学和药效学。
Pharmacokinet。2008; 47(8): 515 - 31所示。
- PubMed ID
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18611061 (在PubMed]
- 文摘
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Aliskiren是第一个口服生物利用率直接肾素抑制剂批准用于治疗高血压。它在激活肾素-血管紧张素-醛固酮系统,或肾素系统,抑制血管紧张肽原的转换由肾素血管紧张素I,从而减少血管紧张素II的形成,血管紧张素转换酶(ACE)和ACE-independent通路。Aliskiren人类肾素是一种高度有效的抑制剂在体外(Aliskiren浓度产生50%抑制肾素0.6 nmol / L)。Aliskiren口服后迅速吸收,最大血浆浓度在1 - 3小时内到达。aliskiren的绝对生物利用度为2.6%。aliskiren血浆蛋白质适中的绑定(47 - 51%)和浓度无关。一旦吸收,aliskiren消除毒品和通过肝胆的路线不变,某种程度上,通过氧化代谢细胞色素P450 (CYP) 3 a4。阿利克仑占大约80%的这种新药中的一种不变的等离子体口服后,表明低接触代谢物。的两个主要氧化代谢物阿利克仑占不到5%的这种新药中的一种等离子体时的最大浓度。Aliskiren通过胆汁排泄几乎完全/粪便路线; 0.6% of the dose is recovered in the urine. Steady-state plasma concentrations of aliskiren are reached after 7-8 days of once-daily dosing, and the accumulation factor for aliskiren is approximately 2. After reaching the peak, the aliskiren plasma concentration declines in a multiphasic fashion. No clinically relevant effects of gender or race on the pharmacokinetics of aliskiren are observed, and no adjustment of the initial aliskiren dose is required for elderly patients or for patients with renal or hepatic impairment. Aliskiren showed no clinically significant increases in exposure during coadministration with a wide range of potential concomitant medications, although increases in exposure were observed with P-glycoprotein inhibitors. Aliskiren does not inhibit or induce CYP isoenzyme or P-glycoprotein activity, although aliskiren is a substrate for P-glycoprotein, which contributes to its relatively low bioavailability. Aliskiren is approved for the treatment of hypertension at once-daily doses of 150 mg and 300 mg. Phase II and III clinical studies involving over 12,000 patients with hypertension have demonstrated that aliskiren provides effective long-term blood pressure (BP) lowering with a good safety and tolerability profile at these doses. Aliskiren inhibits plasma renin activity (PRA) by up to 80% following both single and multiple oral-dose administration. Similar reductions in PRA are observed when aliskiren is administered in combination with agents that alone increase PRA, including diuretics (hydrochlorothiazide, furosemide [frusemide]), ACE inhibitors (ramipril) and angiotensin receptor blockers (valsartan), despite greater increases in the plasma renin concentration. Moreover, PRA inhibition and BP reductions persist for 2-4 weeks after stopping treatment, which is likely to be of benefit in patients with hypertension who occasionally miss a dose of medication. Preliminary data on the antiproteinuric effects of aliskiren in type 2 diabetes mellitus suggest that renoprotective effects beyond BP lowering may be possible. Further studies to evaluate the effects of aliskiren on cardiovascular outcomes and target organ protection are ongoing and will provide important new data on the role of direct renin inhibition in the management of hypertension and other cardiovascular disease.
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- 药物
- 药物酶
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药物 酶 类 生物 药理作用 行动 Aliskiren 细胞色素P450 3 a4 蛋白质 人类 没有底物细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
