Sites of elimination and pharmacokinetics of recombinant [131I]lepirudin in baboons

• Published in: Journal of pharmaceutical sciences Vol. 88; no. 5; pp. 523 - 529
• Main Authors: Meiring, S.M., Lötter, M.G., Badenhorst, P.N., Bucha, E., Nowak, G., Kotzé, H.F.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.05.1999; John Wiley & Sons, Inc; Wiley; American Pharmaceutical Association
• Subjects: Animals; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Fibrinolytic Agents - pharmacokinetics; Half-Life; Hirudins - analogs & derivatives; Hirudins - pharmacokinetics; Immunohistochemistry; Iodine Radioisotopes; Kidney - metabolism; Male; Medical sciences; Papio; Partial Thromboplastin Time; Pharmacology. Drug treatments; Recombinant Proteins - pharmacokinetics; Immunohistochemistry; Intravenous administration; Elimination; Monkey; Metabolism; Antiplatelet agent; Kidney; Blood plasma; Vertebrata; Mammalia; Urinary system; Polypeptide; Animal; Distribution; Primates; Pharmacokinetics; Radiopharmaceuticals; Labelled compound; Lepirudin
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js980407q

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.