tcsc0364 Sitaxsentan (sodium)

Sitaxsentan (sodium) is an orally active, highly selective antagonist of endothelin A receptors.

In Vitro: Sitaxsentan and Bosentan attenuate NTCP transport at higher concentrations, and inhibit human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting. Only sitaxsentan decreased OATP transport (52%)^[1]. Sitaxsentan and sitaxsentan combined with sildenafil completely prevent the increased expressions of endothelin-1 and of the ETB receptor. Sitaxsentan alone partially restores the expressions of BMPR-1A and BMPR-2. The combination of sildenafil and sitaxsentan further restores the expressions of BMPR-1A and BMPR-2, which remaines, however, decreased compared with controls^[3].

In Vivo: Sitaxsentan (5 mg/kg infused iv 10 min prior to onset of hypoxia) completely blocks hypoxia-induced vasoconstriction and this group does not differ from air controls. Oral administration of sitaxsentan, significantly attenuates the increase in MPAP, while the administration of sitaxsentan to rats exposed to normal oxygen levels is without effect on MPAP^[2]. Sitaxsentan alone limits shunt-induced increase in MT. Sitaxsentan combined with sildenafil more effectively prevents this remodeling, which, however, tends to remain increased compared with controls^[3].