Pharmacokinetics, effect on clotting tests and assessment of the immunogenic potential of hirudin after a single subcutaneous or intravenous bolus administration in man.
The pharmacokinetics and the anticoagulant effects of hirudin were investigated in 12 healthy volunteers after single subcutaneous or intravenous bolus administrations. Hirudin concentrations in citrated plasma and urine were determined with a radioimmunobioassay, which detects the inhibitor by its thrombin-binding capacity. Plasma profiles could be adequately described by the equation for an open two-compartment model (intravenous route) and by the Bateman equation (subcutaneous route), respectively. Within 24 h half of the administered hirudin dose was recovered in the urine in biologically active form. The prolongation of clotting times (activated partial thromboplastin and thrombin time) was dependent on the hirudin plasma concentration. All test subjects tolerated the hirudin injection without visible or measurable side effects. No hirudin-specific antibodies were found after single parenteral administrations.
Bichler
J
J
Abteilung für Klinische Chemie und Klinische Biochemie, Chirurgischen Klinik Innenstadt, Universität München.
Siebeck
M
M
Fichtl
B
B
Fritz
H
H
D001681:Biological Assay; D001777:Blood Coagulation / Q000187:drug effects; D001825:Body Fluid Compartments; D006207:Half-Life; D006629:Hirudins / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008657:Metabolic Clearance Rate; D010314:Partial Thromboplastin Time; D011863:Radioimmunoassay; D013917:Thrombin / Q000037:antagonists & inhibitors; D013918:Thrombin Time
D006629:Hirudins; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D013917:Thrombin