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.

Successful Use of Recombinant Hirudin and Its Monitoring by Ecarin Clotting Time in Patients with Heparin-Induced Thrombocytopenia Undergoing Off-Pump Coronary Artery Revascularization

“…This IgG activates platelets in the presence of pharmacologic concentrations of heparin 10–15 . The pharmacokinetics of hirudin in laboratory animals was found to be similar to humans 16–21 . The renal clearance of hirudin approximates the renal clearance of creatinine suggesting clearance by glomerular filtration.…”

Pharmacokinetics Study of Recombinant Hirudin in the Plasma of Rats Using Chromogenic Substrate, ELISA, and Radioisotope Assays

“…Richter et al [9] reported the t 1/2β was 65 min for rats and 56.6 min for dog by using the 125 I-rH combined with thrombin titration assay. The t 1/2β of rH in baboons was determined as 24 min and 23 min by using the 131 I-labeled rH combined the ecarin Clotting Time (ECT) method by Meiring et al [13]. Recently, Huang et al [8] reported that in rats, the t 1/2β was 172.8 min by the total plasma 125 I-labeled rH radioactivity (RA) method and 107 min by the trichloroacetic acid precipitate plasma 125 I-labeled rH radioactive activity (TCA-RA) method.…”