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

Lepirudin has a short half-life, and only 50-60% of the intravenously admin istered dose is excreted by the kidneys. The fate of the remainder is unkno wn, We designed a study to determine the fate of this lepirudin. In each of six baboons, [I-131]lepirudin was given intravenously as a bolus or infuse d over 30 min, 24 h apart. The in vivo redistribution of [I-131]lepirudin w as determined and quantified by scintillation camera imaging, In all studie s, the half-life of [I-131]lepirudin, as determined from the disappearance of radioactivity, was 21 +/- 3 min. The half-life determined from the disap pearance of lepirudin, measured by the Ecarin Clotting Time (ECT) method, w as 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 1 8 +/- 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 d ifferent. In both studies, between 50 and 60% of the administered lepirudin was excreted by the kidney. Studies on sacrificed baboons showed that appr eciable amounts of lepirudin were present in the bile, indicating the liver as a contributor to the elimination of lepirudin.