Preparation of dextran-bound recombinant hirudin and its pharmacokinetic behaviour.

Recombinant desulphatohirudin was bound via lysine residues to oxidized dextrans. The hirudin-dextran conjugates inhibit thrombin like free hirudin. The Ki-values are in the same range. In rabbits and rats the pharmacokinetic behaviour following i.v. administration of these conjugates was examined in comparison to that of hirudin. The hirudin-dextran conjugates were more slowly eliminated than hirudin, the distribution volumes in steady-state were significantly reduced, and, in comparison to hirudin, 5 to 15 times larger areas under the plasma concentration-time-curves were obtained.