Pharmacokinetics of recombinant activated factor VII (rFVIIa)

Recombinant coagulation factor VIIa (NovoSeven(R), Novo Nordisk Pharmaceuti cals, Inc., Princeton NJ, USA) is a new drug for treatment of bleeding in p atients with hemophilia and inhibitors. The pharmacokinetic profiles of rFV IIa have been evaluated in healthy adult volunteers who were pretreated wit h acenocoumarol, in adult and pediatric patients with hemophilia A or B, an d in adult patients with cirrhosis and a prolonged prothrombin time (PT). T he clearance (CL) and half-life (t(1/2)) values of rFVIIa after bolus injec tion mere in the same range in the adult populations studied: patients with hemophilia, patients with cirrhosis, and healthy volunteers. The volume of distribution at steady state (V-ss), on the other hand, was slightly small er in healthy adult volunteers than in patients with hemophilia. The pharma cokinetic profile of rFVIIa seems to be independent of bleeding or nonbleed ing conditions in adult hemophilic patients; however, the patients in these studies did not suffer from major bleeding episodes. The values of CL and t(1/2) were also dose independent in adult patients with hemophilia and in patients with cirrhosis. Pediatric patients with hemophilia had shorter t(1 /2) and higher CL values than the adults with hemophilia. The administratio n of rFVIIa by continuous infusion is still experimental and a number of pr actical issues remain to be resolved.