Small molecular direct thrombin inhibitors (smDTIs) are non-peptide small molecules that specifically and reversibly inhibit both free and clot-bound thrombin by binding to the active site of the thrombin molecule. They prevent VTE in patients undergoing hip- and knee replacement surgery. The advantages of this type of DTIs are that they do not need monitoring, have a wide therapeutic index and the possibility of oral administration route. They are theoretically more convenient than both vitamin K antagonist and LMWH. Researches will, however, have to show the indication of the use and their safety.
The smDTIs where derived using a peptidomimetic design with either P1 residue from arginine itself (e.g. argatroban) or arginine-like substrates such as benzamidine (e.g. NAPAP).