Correspondence: James R Klinger Division of Pulmonary Sleep and Critical Care Medicine, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 Tel +1 401 444 2776 Fax +1 401 444 3002 Email [email protected] Abstract: Ambrisentan is an endothelin receptor antagonist (ERA) that was recently approved for treatment of pulmonary arterial hypertension (PAH). Endothelin (ET) is a potent va...

INTRODUCTION In patients with systemic sclerosis (SSc), digital ischemia results from an occlusive microvasculopathy that may not respond adequately to conventional vasodilators. Endothelin receptor antagonists can potentially modify the fibroproliferative vascular remodeling in SSc, and hence their use may be justified in the management of digital ischemia. The objective of this clinical trial...

BACKGROUND Inhibition of the transporter-mediated hepatobiliary elimination of bile salts is a putative mechanism for liver toxicity observed with some endothelin receptor antagonists (ERAs). METHODS Sandwich-cultured human hepatocytes were used to study the hepatobiliary distribution and accumulation of exogenous taurocholate, ERAs and endogenous bile acids. The molecular mechanisms for find...

Drug-induced liver injury has been observed in patients treated with the endothelin receptor antagonists sitaxentan and bosentan, but not following treatment with ambrisentan. The aim of our studies was to assess the possible role of multiple contributory mechanisms in this clinically relevant toxicity. Inhibition of the bile salt export pump (BSEP) and multidrug resistance-associated protein 2...

It is believed that simultaneous targeting of two or more of the three pathogenic pathways of pulmonary arterial hypertension (the endothelin, nitric oxide, and prostacyclin pathways) is associated with additive or synergistic effects with subsequent increasing efficacy and improving outcomes. However, there is lack of evidence to guide the use of combination strategy among pulmonary arterial h...

A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Ambrisentan (AMB) and Tadalafil (TADA) drug substances in the fixed dosage strength of 10 mg and 40 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) with a mobile phase composed of met...

A growing body of evidence suggests that exercise pulmonary hypertension (ePH) is an early form of pulmonary arterial hypertension (PAH). Identifying the disease at an early, potentially more responsive phase, and initiating treatment may improve functional status and prevent progression to severe forms of PAH. This was a single-center, open-label six-month treatment trial to evaluate the effec...

The present study aimed to characterize comparatively endothelin-1 (ET-1) receptors in rat tissues by radioligand binding assay using [(125)I]ET-1 and to examine receptor binding after oral administration of bosentan. Significant amount of specific [(125)I]ET-1 binding was detected in the lung, heart, kidney, bladder and cerebral cortex of rats. ET-1, bosentan, ambrisentan, and CI-1020 inhibite...

BACKGROUND Sarcoidosis associated pulmonary hypertension (SAPH) is associated with significant morbidity and mortality. There is a paucity of information concerning therapy for this condition. METHODS We performed a prospective, open-label, proof of concept trial of ambrisentan for SAPH. 21 subjects with SAPH received 5 mg/day of ambrisentan for 4 weeks and then 10/mg day for 20 subsequent we...