Pharmacokinetics of recombinant activated factor VII (rFVIIa)

Recombinant coagulation factor VIIa (NovoSeven, Novo Nordisk Pharmaceuticals, Inc., Princeton NJ, USA) is a new drug for treatment of bleeding in patients with hemophilia and inhibitors. The pharmacokinetic profiles of rFVIIa have been evaluated in healthy adult volunteers who were pretreated with acenocoumarol, in adult and pediatric patients with hemophilia A or B, and in adult patients with cirrhosis and a prolonged prothrombin time (PT). The clearance (CL) and half-life (t1/2) values of rFVIIa after bolus injection were 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 (Vss), on the other hand, was slightly smaller in healthy adult volunteers than in patients with hemophilia. The pharmacokinetic profile of rFVIIa seems to be independent of bleeding or nonbleeding conditions in adult hemophilic patients; however, the patients in these studies did not suffer from major bleeding episodes. The values of CL and t1/2 were also dose independent in adult patients with hemophilia and in patients with cirrhosis. Pediatric patients with hemophilia had shorter t1/2 and higher CL values than the adults with hemophilia. The administration of rFVIIa by continuous infusion is still experimental and a number of practical issues remain to be resolved.