Because of high mortality caused by @entity65 , various fibrinolytic agents with diverse pharmacokinetic and pharmacodynamic properties have been developed. A novel mutated chimeric @entity2435 (mt-PA) was developed by the removal of first three domains of @entity2435 , insertion of @entity23854 sequence and mutation towards resistance to @entity2630 ( @entity2630 ). 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 @entity35 . 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 (AUC0 >    ) increased. The elimination half-life (t1/2) 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 ( @entity5976 ) 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.

Scale up and pharmacokinetic study of a novel mutated chimeric @entity2435 (mt-PA) in XXXX .

@entity2630 :: ('24617(Tax:10116)', 'Gene') :: ['PAI-1', 'plasminogen activator inhibitor-1'] @entity23854 :: ('84022(Tax:10116)', 'Gene') :: ['GHRP'] @entity2435 :: ('25692(Tax:10116)', 'Gene') :: ['t-PA', 'tissue plasminogen activator'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular diseases'] @entity5976 :: ('361422(Tax:10116)', 'Gene') :: ['CLp']
@entity35 :: (10116,Species) :: ['rats']
