Academic Journal
Scale up and pharmacokinetic study of a novel mutated chimeric tissue plasminogen activator (mt-PA) in rats
| العنوان: | Scale up and pharmacokinetic study of a novel mutated chimeric tissue plasminogen activator (mt-PA) in rats |
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| المؤلفون: | Raigani, Mozhgan, Rouini, Mohammad-Reza, Golabchifar, Ali-Akbar, Mirabzadeh, Esmat, Vaziri, Behrouz, Barkhordari, Farzaneh, Davami, Fatemeh, Mahboudi, Fereidoun |
| المصدر: | Scientific Reports ; volume 7, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2017 |
| الوصف: | Because of high mortality caused by cardiovascular diseases, various fibrinolytic agents with diverse pharmacokinetic and pharmacodynamic properties have been developed. A novel mutated chimeric tissue plasminogen activator (mt-PA) was developed by the removal of first three domains of t-PA, insertion of GHRP sequence and mutation towards resistance to plasminogen activator inhibitor-1 (PAI-1). Mt-PA protein was expressed in Expi293F cells. The expression level of mt-PA was found to be 5000 IU/mL. Following purification, the pharmacokinetic properties of mt-PA were evaluated in three doses in rats. Data related to mt-PA were best fitted to two compartment model. With the increase in dose, the Area Under the plasma concentration-time Curve (AUC 0→∞ ) increased. The elimination half-life (t 1/2 ) of mt-PA was in the range of 19.1–26.1 min in three doses while that of Alteplase was 8.3 min. The plasma clearance (CLp) of mt-PA ranged from 3.8 to 5.9 mL/min in three doses, which was several times lower than that of Alteplase (142.6 mL/min). The mean residence time (MRT) of mt-PA ranged from 23.3–31.8 min in three doses, which was 4–5 times greater than that of Alteplase (6 min). Mt-PA showed extended half-life and mean residence time and is a good candidate for further clinical studies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/srep43028 |
| الاتاحة: | http://dx.doi.org/10.1038/srep43028 https://www.nature.com/articles/srep43028 https://www.nature.com/articles/srep43028.pdf |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.24A545E5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/srep43028 |
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