title: Sites of elimination and pharmacokinetics of recombinant [131I]lepirudin in baboons.
abstract: Lepirudin has a short half-life, and only 50-60% of the intravenously administered dose is excreted by the kidneys. The fate of the remainder is unknown. We designed a study to determine the fate of this lepirudin. In each of six baboons, [131I]lepirudin was given intravenously as a bolus or infused over 30 min, 24 h apart. The in vivo redistribution of [131I]lepirudin was determined and quantified by scintillation camera imaging. In all studies, the half-life of [131I]lepirudin, as determined from the disappearance of radioactivity, was 21 +/- 3 min. The half-life determined from the disappearance of lepirudin, measured by the Ecarin Clotting Time (ECT) method, was similar at 23 +/- 8 min. Results obtained with the labeled lepirudin are therefore comparable with those obtained using the plasma concentration of lepirudin. When lepirudin was administered as a bolus, the half-life was 18 +/- 4 min, and lepirudin was cleared from the plasma at a rate of 42 +/- 12 mL/min and by the kidneys at 23 +/- 2 mL/min. Following infusion over 30 min, the half-life and total and renal clearances were not significantly different. In both studies, between 50 and 60% of the administered lepirudin was excreted by the kidney. Studies on sacrificed baboons showed that appreciable amounts of lepirudin were present in the bile, indicating the liver as a contributor to the elimination of lepirudin.
authors.affiliation: Department of Haematology and Cell Biology, University of the Orange Free State, P.O. Box 339 (G2), Bloemfontein, Republic of South Africa.
authors.forename: S M
authors.initials: SM
authors.lastname: Meiring
authors.forename: M G
authors.initials: MG
authors.lastname: Lötter
authors.forename: P N
authors.initials: PN
authors.lastname: Badenhorst
authors.forename: E
authors.initials: E
authors.lastname: Bucha
authors.forename: G
authors.initials: G
authors.lastname: Nowak
authors.forename: H F
authors.initials: HF
authors.lastname: Kotzé
mesh_terms: D000818:Animals; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics*; D006207:Half-Life; D006629:Hirudins / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D008297:Male; D010215:Papio; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000493:pharmacokinetics
chemical_list: D005343:Fibrinolytic Agents; D006629:Hirudins; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; C083544:lepirudin