Stabilized Hirudin Activity and Unit-Dose Uniformity in a Dry Premix: Translational Evidence from Venous Thrombosis and Thromboembolism Trials

Recombinant hirudins have been tested clinically in the treatment and prevention of venous thromboembolism. We evaluated the activity retention and unit-dose performance of a low-water-activity hirudin premix, then reviewed randomized evidence from deep-vein thrombosis (DVT) treatment and postoperative prophylaxis. Optimized BCLC® premixes retained 90.6-92.1% antithrombin activity. Activity-distribution RSD was 3.8-4.7%, and capsule fill-weight RSD was 2.9-3.4%. Removal of staged protective mixing or humidity control increased variability and reduced retention. In parenteral studies, subcutaneous recombinant hirudin was compared with intravenous heparin in acute lower-limb DVT. After hip replacement, desirudin reduced confirmed DVT relative to unfractionated heparin (7% vs 23%) and major thromboembolic events relative to enoxaparin (4.9% vs 7.6%). These trials describe systemic hirudin pharmacology; the premix results describe the manufacturing controls required before oral exposure can be studied.