Emerging inhaled bronchodilators: an update

Abstract

Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field.The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients.A variety of b 2 -agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development.The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.

Special Consideration in Treating Patients of Overlap Between Asthma and COPD

“…Recent popular bronchodilators are  2 -agonists with long action duration (long acting  2 -agonist, LABA) such as salmeterol and formoterol, which last for over 12 hours. There are now several even longer-acting  2 -agonists (ultra-LABA) in development, including indacaterol, carmoterol, GW-642444, and BI-1744, which have a duration of action >24 hours and are suitable for once daily use (Cazzola & Matera, 2009). A once daily muscarinic antagonist, tiotropium bromide, is less effective as a bronchodilator in asthma than the  2 -agonists and is used predominantly in COPD, but might be a useful addon therapy in some patients with severe asthma (H.W.…”

Progress and Prospects for Long-Acting Β 2 -Agonists in the Treatment of Chronic Obstructive Pulmonary Disease (Copd)

“…We pointed out that «the oncedaily dosing of a LABA would be a significant convenience and probably a compliance-enhancing advantage, leading to improved overall clinical outcomes in patients with asthma and COPD». Apparently, at that time several ultra LABAs (arformoterol, carmoterol, indacaterol, GSK-159797 (milveterol), GSK-597901, GSK-159802, GSK-642444 (vilanterol) and GSK-678007) were under development.In 2007, we highlighted that arformoterol was not a real once daily LABA and also stressed that «Any company planning to develop a new ultra-LABA must consider very carefully the pharmacological characteristics of the β 2 -adrenoceptor agonist component to understand how it will fit into current treatment strategies and whether it should be used only in combination with other drugs» [2].In 2009, we included in the list of new β 2 -agonists under development BI-1744-CL (olodaterol), and LAS100977 (abediterol) [3]. Furthermore, we illustrated the possible development of saligenin-or indolecontaining and adamantyl-derived β 2 -agonists and highlighted that despite this interesting profile of milveterol, it was likely that it would be developed only as a back-up because of the greater therapeutic index of vilanterol, and also the great delay in the development of carmoterol, although it was the oldest of the ultra-LABAs under investigation.…”

“…In 2009, we included in the list of new β 2 -agonists under development BI-1744-CL (olodaterol), and LAS100977 (abediterol) [3]. Furthermore, we illustrated the possible development of saligenin-or indolecontaining and adamantyl-derived β 2 -agonists and highlighted that despite this interesting profile of milveterol, it was likely that it would be developed only as a back-up because of the greater therapeutic index of vilanterol, and also the great delay in the development of carmoterol, although it was the oldest of the ultra-LABAs under investigation.…”

Fluticasione furoate / vilanterol combination (Relvar Ellipta®) in bronchial asthma: a review of clinical trials

“…Практически все современные иГКС (флутиказона пропионат (ФП), беклометазон, мометазон, будесонид) назначаются 2 раза в день. Вместе с тем доказано, что при использовании инга лятора 1 раз в сутки повышается комплаенс и улуч шается эффективность терапии [2].Единственным иГКС с возможностью назначе ния 1 раз в сутки сегодня является флутиказона фу роат* (ФФ). Химическая структура ФФ отличается от структуры ФП, благодаря чему ФФ обладает более высоким сродством к ГКС рецепторам и способен дольше, чем ФП, задерживаться в легочной тка ни [3].…”

“…Практически все современные иГКС (флутиказона пропионат (ФП), беклометазон, мометазон, будесонид) назначаются 2 раза в день. Вместе с тем доказано, что при использовании инга лятора 1 раз в сутки повышается комплаенс и улуч шается эффективность терапии [2].…”