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.
Markwardt
F
F
Institute of Pharmacology and Toxicology, Medical Academy Erfurt, GDR.
Richter
M
M
Walsmann
P
P
Riesener
G
G
Paintz
M
M
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003911:Dextrans / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D008970:Molecular Weight; D010599:Pharmacokinetics; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D003911:Dextrans; D005343:Fibrinolytic Agents; D006629:Hirudins; D011994:Recombinant Proteins; C060225:desirudin