PHARMACOKINETICS OF RECOMBINANT HIRUDIN IN HEMODIALYZED END-STAGE RENAL-FAILURE PATIENTS

Citation
R. Vanholder et al., PHARMACOKINETICS OF RECOMBINANT HIRUDIN IN HEMODIALYZED END-STAGE RENAL-FAILURE PATIENTS, Thrombosis and haemostasis, 77(4), 1997, pp. 650-655
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Peripheal Vascular Diseas
Journal title
ISSN journal
0340-6245
Volume
77
Issue
4
Year of publication
1997
Pages
650 - 655
Database
ISI
SICI code
0340-6245(1997)77:4<650:PORHIH>2.0.ZU;2-U
Abstract
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.