Disposition of a novel recombinant tissue plasminogen activator, delta 2-89 TPA, in mice

The pharmacokinetic characteristics of delta 2-89 tPA, characterized by the deletion of the first 89 amino acids at the NH2-terminus of tPA, were evaluated and compared to those of recombinant tPA (rtPA). When they were administered intravenously to mice, a biexponential disposition curve was observed for both tPAs. The plasma half-lives of lambda 1 and lambda 2 phases of delta 2-89 tPA were 15 minutes and 180 minutes which are significantly higher than those of rtPA. A zymogram of mouse plasma taken at various time intervals showed that delta 2-89 tPA retained fibrinolytic activity up to 30 minutes, whereas rtPA could be detected only up to 5 minutes after injection. Autoradiography revealed that most of 125I-delta 2-89 tPA was associated with plasma protein complex.