Clinical pharmacology of recombinant hirudin.
Pharmacological profiling of recombinant hirudin (r-hirudin) has shown that this selective tight-binding thrombin inhibitor is a potent, well-tolerated anticoagulant. Clinical pharmacological studies were performed in human volunteers after single and repeated doses of 0.1-0.5 mg/kg. Generally, administration of r-hirudin was tolerated without side effects. Thrombin time and partial thromboplastin time were prolonged dependent on the r-hirudin level in plasma. Platelet counts, fibrinogen level and fibrinolytic system remained unchanged. Bleeding time was not prolonged. On intravenous injection, r-hirudin was rapidly distributed into the extracellular space and eliminated, with a dose-dependent half-life of 1-2 h (first-order kinetics). After subcutaneous administration, the rH level in blood reached plateau values within 60-120 min. The high recovery of unchanged r-hirudin in the urine identified renal excretion as the predominant route of r-hirudin clearance.
Markwardt
F
F
Institute of Pharmacology and Toxicology, Medical Academy Erfurt, FRG.
Nowak
G
G
Stürzebecher
J
J
D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects; D006207:Half-Life; D006629:Hirudins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D010314:Partial Thromboplastin Time; D010976:Platelet Count / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors; D013918:Thrombin Time
D006629:Hirudins; D011993:Recombinant Fusion Proteins; D005340:Fibrinogen; D013917:Thrombin