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

Abstract

1. The study aimed to investigate the pharmacokinetics of thrombomodulin alpha (TM-α), human-soluble thrombomodulin in rats.

2. Intravenously administered TM-α was eliminated in two phases (T_1/2α = 0.2–0.3 h and T_1/2β = 6–8 h), and the elimination curve was linear in a dose range of 10–250 μg kg⁻¹. Based on the results of tissue concentration studies after reaching the steady-state, the highest concentration of TM-α was seen in the plasma, suggesting the low levels of transfer to tissues (≤ 22% of plasma levels).

3. In vivo metabolism of TM-α was also analysed using high-performance liquid chromatography. The main peak observed in the plasma was TM-α, 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-α.

4. 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-α will vary considerably in patients with renal impairment.

Keywords::

• Pharmacokinetics
• thrombomodulin alpha
• rat
• renal impairment

Acknowledgements

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.