Hjermitslev Marie, Grimm Daniela G, Wehland Markus, Simonsen Ulf, Krüger Marcus
Department of Biomedicine, Pharmacology, Aarhus University, Aarhus C, Denmark.
Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Basic Clin Pharmacol Toxicol. 2017 Oct;121(4):225-233. doi: 10.1111/bcpt.12800. Epub 2017 Jun 19.
Azilsartan (AZL) medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both in blood pressure (BP) reduction and in tolerability, but has not yet been taken into practice to the same extent as other angiotensin II receptor blockers (ARBs) that have been on the market for a longer period. AZL antagonizes the AT receptor for angiotensin II (ANG II), whereas angiotensin-converting enzyme inhibitors block the conversion of angiotensin I to ANG II, but not alternative routes of formation of ANG II. The bioavailability of AZL is about 60% and it has a t of 1.5-3 hr and a half-life of approximately 11 hr. With its IC of 7.4 nM after 5 hr of drug washout in radioligand assays, AZL has a tighter and longer-lasting binding to the AT receptor by several orders of magnitude than other ARBs, which might lead to a more effective reduction in BP. Clinical studies have revealed that AZL doses of 40 and 80 mg/day reduce BP significantly better than maximal clinical doses of valsartan or olmesartan, while being well tolerated and exhibiting a spectrum of adverse effects comparable to those of other ARBs. These properties of AZL might lower the risk of cardiovascular disease and thereby reduce mortality rates. However, the existing mortality studies have not found this correlation, which should be further investigated.
阿齐沙坦美多昔酯于2011年获美国食品药品监督管理局批准用于治疗高血压，在降低血压和耐受性方面均显示出良好效果，但与其他上市时间更长的血管紧张素II受体阻滞剂（ARB）相比，其应用程度尚未达到相同水平。阿齐沙坦可拮抗血管紧张素II（ANG II）的AT受体，而血管紧张素转换酶抑制剂可阻断血管紧张素I向ANG II的转化，但不能阻断ANG II的其他生成途径。阿齐沙坦的生物利用度约为60%，其达峰时间为1.5 - 3小时，半衰期约为11小时。在放射性配体测定中，药物洗脱5小时后其抑制常数为7.4 nM，与其他ARB相比，阿齐沙坦与AT受体的结合更紧密且持续时间长几个数量级，这可能导致更有效地降低血压。临床研究表明，每日40毫克和80毫克剂量的阿齐沙坦降低血压的效果明显优于缬沙坦或奥美沙坦的最大临床剂量，同时耐受性良好，不良反应谱与其他ARB相当。阿齐沙坦的这些特性可能会降低心血管疾病风险，从而降低死亡率。然而，现有的死亡率研究尚未发现这种相关性，对此应进一步研究。
