Neurological Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, OH, USA.
Eur J Drug Metab Pharmacokinet. 2022 Mar;47(2):165-176. doi: 10.1007/s13318-021-00743-8. Epub 2021 Dec 11.
Desmoteplase is a bat (Desmodus rotundus) saliva-derived fibrinolytic enzyme resembling a urokinase and tissue plasminogen activator. It is highly dependent on fibrin and has some neuroprotective attributes. Intravenous administration of desmoteplase is safe and well tolerated in healthy subjects. Plasma fibrinolytic activity is linearly related to its blood concentration, its terminal elimination half-life ranges from 3.8 to 4.92 h (50 vs. 90 μg/kg dose). Administration of desmoteplase leads to transitory derangement of fibrinogen, D-dimer, alpha2-antiplasmin, and plasmin and antiplasmin complex which normalize within 4-12 h. It does not alter a prothrombin test, international normalized ratio, activated partial thromboplastin time, and prothrombin fragment 1.2. Desmoteplase was tested in myocardial infarction and pulmonary embolism and showed promising results versus alteplase. In ischemic stroke trials, desmoteplase was linked to increased rates of symptomatic intracranial hemorrhages and case fatality. However, data from "The desmoteplase in Acute Ischemic Stroke" Trials, DIAS-3 and DIAS-J, suggest that the drug is well tolerated and its safety profile is comparable to placebo. Desmoteplase is theoretically a superior thrombolytic because of high fibrin specificity, no activation of beta-amyloid, and lack of neurotoxicity. It was associated with better outcomes in patients with significant stenosis or occlusion of a proximal precerebral vessels. However, DIAS-4 was stopped as it might have not reached its primary endpoint. Due to its promising properties, desmoteplase may be added into treatment of ischemic stroke with extension of the time window and special emphasis on patients presenting outside the 4.5-h thrombolysis window, with wake-up strokes and strokes of unknown onset.
地特酶是一种来源于蝙蝠（吸血蝠属）唾液的纤维蛋白溶解酶，类似于尿激酶和组织型纤溶酶原激活物。它高度依赖纤维蛋白，并具有一些神经保护特性。在健康受试者中，静脉给予地特酶是安全且耐受良好的。地特酶的血浆纤维蛋白溶解活性与其血药浓度呈线性相关，其终末消除半衰期为 3.8 至 4.92 小时（50 微克/千克剂量与 90 微克/千克剂量）。给予地特酶可导致纤维蛋白原、D-二聚体、α2-抗纤溶酶和纤溶酶-抗纤溶酶复合物一过性紊乱，这些指标在 4-12 小时内恢复正常。它不会改变凝血酶原试验、国际标准化比值、活化部分凝血活酶时间和凝血酶原片段 1.2。地特酶已在心肌梗死和肺栓塞中进行了测试，与阿替普酶相比显示出有希望的结果。在缺血性脑卒中试验中，地特酶与症状性颅内出血和病死率增加相关。然而，来自“地特酶治疗急性缺血性脑卒中”试验（DIAS-3 和 DIAS-J）的数据表明，该药具有良好的耐受性，其安全性与安慰剂相当。地特酶由于具有高纤维蛋白特异性、不激活β-淀粉样蛋白和无神经毒性，因此理论上是一种更优越的溶栓药。它与近端大脑前血管存在显著狭窄或闭塞患者的更好结局相关。然而，DIAS-4 试验被停止，因为它可能没有达到主要终点。由于其有前途的特性，地特酶可能会被添加到缺血性脑卒中的治疗中，延长治疗时间窗，并特别关注不在 4.5 小时溶栓时间窗内的患者，包括醒来时发生的脑卒中及发病原因不明的脑卒中。
