Pharmacokinetics and pharmacodynamics of hirudin in man after single subcutaneous and intravenous bolus administration.

The pharmacokinetics (half-life time of absorption and elimination, total clearance, distribution volume etc.), effects on hemostasis (clotting times, blood cell counts) and renal excretion of hirudin were investigated on healthy volunteers after single subcutaneous (600, 800 or 1000 antithrombin units (AT-U)/kg; n = 3 per each dose) or intravenous (1000 AT-U/kg; n = 3) injections. Hirudin concentrations in citrated plasma and urine were determined by means of a radioimmunobioassay, whereby the inhibitor is detected by its thrombin binding capacity. Plasma profiles were adequately described by the Bateman equation (subcutaneous injection) and by an open two-compartment model (intravenous injection), respectively. Within 24 h about half of the applied hirudin dose was renally excreted in active form. The prolongation of clotting times (thrombin time, partial thromboplastin time (PTT), Quick) was dependent on the hirudin plasma level. The PTT proved to be the most reliable test for representation of the actual inhibitor plasma concentrations. Generally, the blood cell counts were unchanged by the hirudin administration. All test subjects tolerated the hirudin injection without visible or measurable side effects.