PHARMACOLOGY OF R-HIRUDIN IN RENAL IMPAIRMENT

The pharmacokinetic properties of r-hirudin were studied in nine patients suffering from different degrees of renal insufficiency. To this end, r-hirudin was administered intravenously at dosages of 0.1 mg/kg. The elimination half-life t1/2-beta was determined in blood plasma and the cumulative r-hirudin excretion in urine was measured over 48 h. In healthy volunteers t1/2-beta was 0.9 +/- 0.2 h; the cumulative r-hirudin excretion in urine after 48 h amounted to 38 +/- 10 % of the dose administered, most of this quantity was excreted during the first hours. In seven patients with chronic renal failure, t1/2-beta was 15 to 41 h: in three of these patients cumulative urinary r-hirudin excretion was increased to 70 - 80 %, in four patients cumulative r-hirudin excretion in urine within 48 h amounted to 39 +/- 8 %, but was delayed in time. In 2 bilaterally nephrectomized patients, t1/2-beta was 168 and 316 h, resp. The renal clearance of hirudin was significantly and linearly con-elated with the creatinine clearance (r= 0.872). In all patients aPTT and bleeding time were only moderately prolonged. Because of the modified pharmacokinetic behaviour the administration of hirudin in patients with impaired renal function requires individually adjusted dosages or prolonged administration intervals.