Hirudin as anticoagulant in experimental hemodialysis.
After genetically engineered recombinant DNA desulfatohirudin (r-hirudin) had been investigated as to its pharmacokinetic behavior and blood level course in nephrectomized dogs, the compound was studied for its capability to prevent thrombus formation in the extracorporeal circulation. Beagle dogs underwent bilateral functional nephrectomy followed by experimental hemodialysis. r-Hirudin content in blood, fibrinogen level as well as platelet count were determined before and during the dialysis. Furthermore, the blood loss during the experiment was measured as well as the mean arterial pressure and the pressure in the blood line system. Intravenous administration of the thrombin inhibitor resulted in initial distribution in the extracellular space (distribution phase 90 min) followed by retarded decrease of the r-hirudin blood level (t1/2 beta approximately 6-8 h) which is due to the missing renal excretion of the inhibitor. This caused a long-lasting, dose-dependent anticoagulant effect, which is not only characterized by the prevention of increasing pressure before the capillary dialyzer but also by the reduced drop in fibrinogen and platelets during hemodialysis. The required dose of r-hirudin (0.5 mg/kg) is within a range where bleeding complications will not occur yet.
Markwardt
F
F
Institute of Pharmacology and Toxicology, Medical Academy Erfurt, FRG.
Nowak
G
G
Bucha
E
E
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D016063:Blood Loss, Surgical; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D006435:Renal Dialysis / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D005340:Fibrinogen; C060225:desirudin