COPD and asthma - arformoterol
The incidence of chronic obstructive pulmonary disease, or COPD, is rising, and there is a great need for more effective treatments. COPD includes emphysema and chronic bronchitis, and mortality and morbidity levels are substantial.
The incidence of chronic obstructive pulmonary disease, or COPD, is rising, and there is a great need for more effective treatments. COPD includes emphysema and chronic bronchitis, and mortality and morbidity levels are substantial.
Patients suffer from an irreversible obstruction of the flow of air within their lungs as well as inflammation, and ß-adrenoceptor agonists are commonly used to treat it, as with asthma, because they have a bronchodilating effect.
Many of these are short acting, such as salbutamol, which are useful in relieving acute exacerbations. But for chronic disease, longer acting agents such as formoterol are used, often in combination with corticosteroids, to prevent exacerbations and improve lung function. However, their long-term use also increases the risk of death.
Most of these long-acting agents are racemic, and it has now been established that the R enantiomer is far more active than the S, which is largely responsible for the negative effects. As a result, Sepracor has been developing arformoterol, the R enantiomer of formoterol, for treating COPD and asthma.1
Several trials have been carried out. In one, 31 asthmatic adults were given single nebulised doses of 12, 24, 48 or 72µg arformoterol, placebo or 2.5µg salbutamol on separate days.2 The peak change in forced expiratory volume was better for all doses of arformoterol, and no different from salbutamol, with a similar onset of action. Twenty-four hours after dosing, the FEV was significantly greater for those given the two higher doses of arformoterol than those given salbutamol, and the incidence of exacerbations and need for rescue medication was better at all doses of arformoterol than either placebo or salbutamol.
A randomised double-blind, double dummy study has also been carried out.3 Single nebulised doses of the racemic drug (4.5 or 36µg), arformoterol (2.25 or 18µg), the S-isomer (18µg) or placebo were given to 46 patients with asthma. Those given high doses of arformoterol or the racemate experienced bronchodilation lasting up to 24 hours after dosing. The S isomer had no effect.
It has also been compared to the long acting ß2-adrenoceptor agonist salmeterol in patients with COPD.4 Nebulised doses were given of 9.6, 48 or 96µg once a day, 24µg twice a day or placebo, and then open label salmeterol in doses of 42µg twice a day. All except the lowest dose of arformoterol gave long lasting bronchodilation, and the US FDA has recently approved the drug, under the brand name Branova, for treating COPD.