Pharmacokinetics of recombinant hirudin in hemodialyzed end-stage renal failure patients.
Recently, hirudin was used for the first time as an anticoagulant during hemodialysis in men. Pharmacokinetic data of this compound in end-stage renal failure are however not available. In this study, the pharmacokinetics of recombinant hirudin (HBW 023) was evaluated in hemodialysis-treated end-stage renal failure patients. HBW 023 was administered 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. The initial dialysis (HD1) was performed with a low flux polysulfone dialyzer, the following dialyses (up to HD6) with a high flux polysulfone 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 HD1, and then gradually decreased to 15.2 +/- 15.2 ng/ml at the end of HD6. Pharmacokinetic data were compared to those obtained in healthy controls (n = 5), receiving the same dose, and reaching the same peak hirudin level. 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 curve 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 +/- 2.01, p < 0.05). Hirudin disappearance rate was the same during high flux polysulfone dialysis as during interdialytic periods. Hirudin removal was markedly higher in those patients still maintaining some residual renal function and parameters of hirudin removal were significantly correlated to residual creatinine clearance. It is concluded that hirudin removal from the body is markedly depressed in hemodialyzed end-stage renal failure patients and that even minor residual renal function may increase this removal rate.
Vanholder
R
R
Nephrology Department, University Hospital, Gent, Belgium.
Camez
A
A
Veys
N
N
Van Loo
A
A
Dhondt
A M
AM
Ringoir
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000493:pharmacokinetics*; D016022:Case-Control Studies; D005260:Female; D006207:Half-Life; D006629:Hirudins / Q000493:pharmacokinetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood / Q000628:therapy
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins