부산대학교 도서관

Aims: TMS‐007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen‐fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti‐inflammatory action, mediated by soluble epoxide hydrolase inhibition, may contribute to its efficacy. Evidence suggests that TMS‐007 can effectively treat experimental thrombotic and embolic strokes with a wide time window, while reducing haemorrhagic transformation. We aim to evaluate the safety, pharmacokinetics and pharmacodynamics of TMS‐007 in healthy volunteers. Methods: This was a randomized, placebo‐controlled, double blind, dose‐escalation study, administered as a single intravenous infusion of TMS‐007 in cohorts of healthy male Japanese subjects. Six cohorts were planned, but only five were completed. In each cohort (n = 8), individuals were randomized to receive one of five doses of TMS‐007 (3, 15, 60, 180 or 360 mg; n = 6) or placebo (n = 2). Results: TMS‐007 was generally well tolerated, and no serious adverse events were attributed to the drug. A linear dose‐dependency was observed for plasma TMS‐007 levels. No symptoms of bleeding were observed on brain MRI analysis, and no bleeding‐related responses were found on laboratory testing. The plasma levels of the coagulation factor fibrinogen and the anti‐fibrinolysis factor α2‐antiplasmin levels were unchanged after TMS‐007 dosing. A slight increase in the plasma level of plasmin‐α2‐antiplasmin complex, an index of plasmin formation, was observed in the TMS‐007 group in cohort 2. Conclusions: TMS‐007 is generally well tolerated and exhibits favourable pharmacokinetic profiles that warrant further clinical development. [ABSTRACT FROM AUTHOR]