Paton D P
Professor Emeritus of Pharmacology, University of Auckland, Auckland, New Zealand and Professor Emeritus of Oral Biology, Edmonton, Alberta, Canada.
Drugs Today (Barc). 2020 Oct;56(10):643-654. doi: 10.1358/dot.2020.56.10.3182908.
Osilodrostat was synthesized in a search for a drug that would inhibit the synthesis of aldosterone, with the aim to discover a new approach for treating hypertension. However, early clinical trials revealed that the doses that could be used for this purpose were limited because osilodrostat was also inhibiting the synthesis of cortisol. Osilodrostat is in fact an inhibitor of both the cytochrome P450 (CYP) enzymes 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) and thus inhibits the synthesis of both cortisol and aldosterone. Subsequent clinical trials have established that it can be used very effectively in Cushing's disease caused by a functioning tumor of the pituitary gland in patients whose condition has not been adequately treated by surgery or who are not candidates for such surgery.
奥西卓司他是在寻找一种能抑制醛固酮合成的药物过程中合成的，目的是发现一种治疗高血压的新方法。然而，早期临床试验表明，可用于此目的的剂量有限，因为奥西卓司他也会抑制皮质醇的合成。事实上，奥西卓司他是细胞色素P450（CYP）酶11β-羟化酶（CYP11B1）和醛固酮合成酶（CYP11B2）的抑制剂，因此会抑制皮质醇和醛固酮的合成。随后的临床试验证实，对于因垂体功能性肿瘤导致的库欣病患者，如果手术治疗效果不佳或不适合手术，奥西卓司他能非常有效地发挥作用。
