Argatroban development

Starting with the known thrombin inhibitors Argatroban and Afx(2-naphthyl-sulfonyl-glycyl)-DL-/>-amidinophenylalanyl-piperidine (NAPAP), a group at Roche initiated a medicinal chemistry program to develop thrombin inhibitors with reduced toxicity and an improved hemodynamic profile [17]. 

The use of unfractionated heparin has been optimized by the development of the LMWHs. This is primarily due to our current understanding of the chemistry and biology of heparin. Antithrombin drugs such as hirudin, argatroban, and bivalirudin have been in development for many years. These drugs are useful as substitutes for heparin in such conditions as heparin-induced thrombocytopenia however, these drugs do not have an antidote and cannot be used for surgical indications at... 

Ikoma H. Development of argatroban as an anticoagulant and antithrombin agent in Japan. Pathophysiol Haemost Thromb 2002 32(Suppl 3) 23-8. 

ARGATROBAN Argatroban, a synthetic compound based on the structure of L-Arg, binds reversibly to the catalytic site of thrombin. Administered intravenously, it has an immediate onset of action and a t j of 40-50 minutes. Argatroban is metabolized by hepatic CYPs and is excreted in the bile therefore dosage reduction is required for patients with hepatic insufficiency. The dosage is adjusted to maintain an aPTT of 1.5-3 times the baseline value. Argatroban can be used as an alternative to lepirudin for prophylaxis or treatment of patients with or at risk of developing heparin-induced thrombocytopenia. 

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