Bosentan Therapy for Pulmonary Arterial Hypertension

Abstract

The endothelin-receptor antagonist bosentan is beneficial in patients with pulmonary arterial hypertension and is well tolerated at a dose of 125 mg twice daily. Endothelin-receptor antagonism with oral bosentan is an effective approach to therapy for pulmonary arterial hypertension.

D-optimal Design for Preparation and Optimization of Fast Dissolving Bosentan Nanosuspension

“…4 Bosentan is an orally active, selective and competitive non-peptide dual endothelin receptor (both ET A and ET B ) antagonist and usually used in cure of PAH. 5 Bosentan is also being considered for treatment of other conditions such as Eisenmenger syndrome, 6 persistent pulmonary hypertension of the newborn, 7 digital ulcer prevention in patients with systemic sclerosis, 8 adolescent and adult patients who have undergone Fontan operation, 9 vascular remodeling and dysfunctional angiogenesis in diabetes 10 and possibly even depression. 11 For treatment of PAH, bosetan is currently administered at the daily dose of 125-250 mg. 12 The maximum plasma peak is seen within 3-5 h after oral intake and the half-life of drug is 5.4 h. 13 Moreover, the bioavailability of bosentan after oral administration is approximately low (50%) 14 and variability is seen in bosentan absorption which may get back to its poor water solubility.…”

International Hypoxia Symposium (13th) for the Publishing of the Conference Proceedings for 2003 Conference

“…Epo plasma levels increase in the first 24-48h of hypoxia exposure (in moderate -1500-3000 m -as well as extreme altitudes >3000 m) up to 2.5 fold and drop back to sea levels within the following three weeks even if the subjects remain at high altitude (107). An increase of 28% in the serum erythropoietin levels was observed in himian subjects after just 2 hours of exposure to hypobaric hypoxia (lO^/oO^ in nitrogen) (87).…”

“…Moreover, epoprostenol costs ~ CAN $100,000/ year. Bosentan is administered orally, but its effectiveness is limited (patients on bosentan walk only 43 meters longer in a 6 minute walk compared to patients on placebo), and it not infrequently causes a dose-dependent liver toxicity (107). Bosentan costs ~ CAN$55,000/ year.…”

Pulmonary Arterial Hypertension in Connective Tissue Diseases

“…Бозентан, неселективный ингибитор эндотелино-вых рецепторов, в трех рандомизированных контролиру-емых исследованиях продемонстрировал свою эффектив-ность у пациентов с ЛАГ [33,34]. Бозентан был первым зарегистрированным для пациентов с ССД препаратом для лечения ЛАГ.…”

“…При анализе подгруппы пациентов с ССД в исследовании BREATH-1 16-недельная терапия бозентаном предотвра-тила ухудшение в 6МТХ с увеличением на 3 м в контроль-ной группе, по сравнению с уменьшением на 40 м в группе плацебо [34]. Открытое исследование с внутривенной те-рапией эпопростенолом (в дозе 11,2 нг/кг в 1 мин в течение 12 нед) продемонстрировало увеличение дистанции 6-ми-нутной ходьбы в среднем на 108 м по сравнению со стан-дартной терапией ЛАГ-СТЗСТ [41].…”