Pharmacokinetics of recombinant human soluble thrombomodulin, thrombomodulin alfa in the rat

The study aimed to investigate the pharmacokinetics of thrombomodulin alpha (TM-), human-soluble thrombomodulin in rats. Intravenously administered TM- was eliminated in two phases (T1/2 = 0.2-0.3 h and T1/2 = 6-8 h), and the elimination curve was linear in a dose range of 10-250 g kg-1. Based on the results of tissue concentration studies after reaching the steady-state, the highest concentration of TM- was seen in the plasma, suggesting the low levels of transfer to tissues ( 22% of plasma levels). In vivo metabolism of TM- was also analysed using high-performance liquid chromatography. The main peak observed in the plasma was TM-, and even 72 h after the last dose of repeated administrations, 80% or more was unchanged form. Approximately half of the radioactivity excreted in the urine was recovered as a peak corresponding to TM-. The results reveal that although plasma clearance was lower in the renally impaired rats, the decrease was not large, with a difference of only about 20%. As a result, although the cause remains unclear, it is considered unlikely that the plasma concentrations of TM- will vary considerably in patients with renal impairment.