Safety, pharmacokinetics, and immunogenicity of single‐dose rFXIII administration to healthy volunteers

摘要: Summary. Background: Factor XIII (FXIII) is a transglutaminase that cross-links fibrin and other proteins to improve clot strength resistance fibrinolysis. Both congenital acquired FXIII deficiency may result in bleeding diathesis, plasma-derived has been used treat many of these clinical conditions. Objectives: A study was designed performed evaluate the safety, pharmacokinetics, immunogenicity recombinant (rFXIII) administration healthy adult volunteers. Patients method: Fifty volunteers were enrolled this randomized, double-blinded, placebo-controlled study. A single dose rFXIII, ranging from 2 U kg−1 50 U kg−1, or placebo administered. Safety evaluated by capturing adverse events, safety laboratory studies, score for deep venous thrombosis. Blood samples taken pharmacokinetic analysis throughout 28-day follow-up period. Results: Recombinant well tolerated, with no serious events dose-related toxicities. Following i.v. injection 50 U kg−1 estimated terminal half-life 270–320 h, volume distribution ranged 40 75 mL kg−1, activity increased 1.77% per 1 U kg−1 rFXIII Increase circulating A2B2 decrease free FXIII-B subunit indicate vivo formation heterotetramer. An immunogenic response yeast, production host, not observed. Conclusions: Recombinant tolerated at doses up The pharmacological immunological profile suggests it should be studied patients as systemic hemostat hemorrhage.