Recently, hirudin was used for the first time as an anticoagulant duri
ng hemodialysis in men. Pharmacokinetic data of this compound in end-s
tage renal failure are however not available. In this study, the pharm
acokinetics of recombinant hirudin (HBW 023) was evaluated in hemodial
ysis-treated end-stage renal failure patients. HBW 023 was administere
d as a bolus at the start of a single dialysis (0.02 to 0.08 mg/kg) in
20 patients, and plasma hirudin levels were followed during this and
the 5 following dialyses, without additional hirudin administration. T
he initial dialysis (HD1) was performed with a low flux polysulfone di
alyzer; the following dialyses (up to HD6) with a high flux polysulfon
e dialyzer and regular heparin. Hirudin levels averaged 504.0 +/- 214.
0 and 527.7 +/- 217.1 ng/ml in the middle and at the end of HD,, and t
hen gradually decreased to 15.2 +/- 15.2 ng/ml at the end of HD6. Phar
macokinetic data were compared to those obtained in healthy controls (
n = 5), receiving the same dose, and reaching the same peak hirudin le
vel. Hirudin half-life was >30 times longer in hemodialysis patients (
51.8 +/- 15.6 vs. 1.7 +/- 1.5 h, p <0.001), whereas area under the cur
ve was >60 times higher (34,669 +/- 14,898 vs. 545 +/- 205 ng/ml X h,
p <0.001). Distribution volume was lower in hemodialysis patients (11.
0 +/- 3.1 vs. 14.1 +/- 2.0 I, p <0.05). Hirudin disappearance rate was
the same during high flux polysulfone dialysis as during interdialyti
c periods. Hirudin removal was markedly higher in those patients still
maintaining some residual renal function and parameters of hirudin re
moval were significantly correlated to residual creatinine clearance.
It is concluded that hirudin removal from the body is markedly depress
ed in hemodialyzed end-stage renal failure patients and that even mino
r residual renal function may increase this removal rate.