Stability of alteplase for ultrasound-facilitated catheter-directed thrombolysis.
Stability of alteplase for ultrasound-facilitated catheter-directed thrombolysis.
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超声导管导向的溶栓的稳定性。
DOI：
10.1182/bloodadvances.2021005001
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发表时间：
2021-12-14
期刊：
影响因子：
7.5
通讯作者：
Goldhaber, Samuel Z.
中科院分区：
文献类型：
--
作者：
Fanikos, John;Marquis, Kathleen;Buckley, Leo;Tran, Lena K.;McLaughlin, Kevin;Golash, Abby Jane;Campia, Umberto;Piazza, Gregory;Connors, Jean M.;Goldhaber, Samuel Z.
在模拟超声辅助导管导向给药期间，阿替普酶溶液随时间稳定降解。剩余的非降解阿替普酶蛋白保留功能活性。超声辅助导管定向溶栓与小剂量阿替普酶联合应用治疗肺栓塞。这降低了较高剂量阿替普酶全身给药伴随的出血风险。一些研究表明，阿替普酶给药2 - 6小时是安全有效的，但几乎没有数据支持阿替普酶在这些条件下的稳定性。因此，我们进行了这项体外研究，以确定阿替普酶的稳定性持续时间。阿替普酶制备为100 mL中8 mg、150 mL中6 mg和200 mL中8 mg的溶液。通过EkoSonic血管内系统（使用和不使用超声）给予溶液，以模拟2、4和6小时内的给药。采用反相高效液相色谱法（RP-HPLC）评估阿替普酶。在模拟输注期间，在时间0和30分钟间隔进行试验。采用酶联免疫吸附试验测量模拟输注期间0时和15分钟间隔时的阿替普酶浓度。通过在无超声条件下使用RP-HPLC，阿替普酶浓度在输注120、240和360分钟内保持在原始浓度的1%范围内。通过使用RP-HPLC进行测量，在超声存在下，阿替普酶随时间稳定降解，在120分钟内降解至其原始量的90%，在240分钟内降解至80%，在360分钟内降解至70%。剩余的阿替普酶可用于酶活性。在模拟超声辅助导管导向给药期间，0.04和0.08 mg/mL阿替普酶溶液随时间稳定降解。不降解的阿替普酶仍然可用于酶活性。
Alteplase solutions degrade steadily over time during simulated ultrasound-facilitated catheter-directed administration. Remaining nondegraded alteplase proteins retained functional activity. Ultrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the risk of bleeding that accompanies systemic administration of higher alteplase doses. Some studies suggest that alteplase given over 2 to 6 hours is safe and effective, but there are few data to support the stability of alteplase under these conditions. Therefore, we undertook this in vitro study to determine the duration of alteplase stability. Alteplase was prepared in solutions of 8 mg in 100 mL, 6 mg in 150 mL, and 8 mg in 200 mL. Solutions were administered through the EkoSonic Endovascular System (with and without ultrasound) to simulate administration over 2, 4, and 6 hours. Alteplase was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). Assays were performed at time 0 and at 30-minute intervals during simulated infusion. An enzyme-linked immunosorbent assay was used to measure alteplase concentrations at time 0 and at 15-minute intervals during simulated infusion. By using RP-HPLC in the absence of ultrasound, the alteplase concentration remained within 1% of the original concentration through 120, 240, and 360 minutes of infusion. By using RP-HPLC for measurement, alteplase in the presence of ultrasound degraded steadily over time to ∼90% of its original amount in 120 minutes, ∼80% in 240 minutes, and ∼70% in 360 minutes. The remaining alteplase was available for enzymatic activity. Alteplase solutions of 0.04 and 0.08 mg/mL degraded steadily over time during simulated ultrasound-facilitated catheter-directed administration. Alteplase that did not degrade remained available for enzymatic activity.
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酶联免疫吸附测定法，用于对植物次生代谢产物的定量/定性分析。
影响因子：
3.3
作者：
Sakamoto S;Putalun W;Vimolmangkang S;Phoolcharoen W;Shoyama Y;Tanaka H;Morimoto S
通讯作者：
Morimoto S
影响因子：
11.3
作者：
Tapson, Victor F.;Sterling, Keith;Goldhaber, Samuel Z.
通讯作者：
Goldhaber, Samuel Z.
DOI：
10.1097/01.rvi.0000147066.97599.87
发表时间：
2005-03-01
影响因子：
2.9
作者：
Smikahl, J;Yeung, D;Semba, CP
通讯作者：
Semba, CP
影响因子：
37.8
作者：
Kucher, Nils;Boekstegers, Peter;Baumgartner, Iris
通讯作者：
Baumgartner, Iris
DOI：
10.1016/j.jstrokecerebrovasdis.2018.05.049
发表时间：
2018-10-01
影响因子：
2.5
作者：
Faine, Brett A.;Dayal, Sanjana;Leira, Enrique C.
通讯作者：
Leira, Enrique C.