Thrombin inhibitor transporters

Walter, E., Kissel, T., Reers, M., Dickneite, G., Hoffmann, D., Stuber, W., Transepithelial transport properties of peptidomimetic thrombin inhibitors in monolayers of a human intestinal cell line (Caco-2) and their correlation to in vivo data, Pharm. Res. 1995, 32, 360-365. 

Sugano et al. studied the membrane permeation of 51 benzamidine-based thrombin inhibitors in a rat everted sac permeability model [197]. They reported significant membrane permeabilities in this in vitro model, which they attributed to passive paracellular transport, a different absorption mechanism to transcellular permeability. 

Very recently, (3-lactam antibiotics have been shown to offer neuroprotection by increasing glutamate transporters expression via gene activation [15] in addition, the discoveries of new biologically active (3-lactams such as cholesterol acyl transferase inhibitors [16-18], thrombin inhibitors [19], human cytomegalovirus protease inhibitors [20], matrix-metallo protease inhibitors [21], inhibitors of human leukocyte elastase (HLE) [22, 23] and cysteine protease [24, 25], and apoptosis inductors [26, 27] have provided much needed motivation for continuous development of new (3-lactam systems. 

Figure 9.14 An example of the use of a prodrug to improve passive transport. Ximelagatran, a double prodrug used to overcome the poor absorption characteristics of the thrombin inhibitor melagatran, requires desterification and hydroxyamidine reduction to generate the active species. ...

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