Enantiomer-Specific Effects of Albuterol on Airway Inflammation in Healthy and Asthmatic Cats

Abstract

Background: Racemic (R,S)-albuterol is a 1:1 mixture of an R-enantiomer which has bronchodilatory and anti-inflammatory effects, and an S-enantiomer which is associated with increased airway hyperreactivity and proinflammatory effects. Proinflammatory effects of regularly inhalated and S-albuterol have not been studied in a whole-animal model. We hypothesized that regular administration of R,S-albuterol or S-albuterol, but not R-albuterol, would induce airway inflammation in healthy and asthmatic cats. Methods: Six healthy and 5 experimentally asthmatic cats were randomized to receive inhaled R,S-albuterol, S-albuterol, R-albuterol, or placebo (saline) twice daily for 2 weeks, followed by a 6-week washout before crossover to the next treatment. Bronchoalveolar lavage fluid was collected for cell counts and cytokine analysis prior to and at the end of each 2-week treatment. Results: Healthy and asthmatic cats receiving R,S- and S-albuterol had higher total lavage cell numbers (p = 0.04 and p = 0.02, respectively) than those receiving R-albuterol and placebo. The number of lavage eosinophils and the TNF-α bioactivity was higher in asthmatic cats receiving R,S- and S-albuterol compared with those receiving the other treatments (p = 0.03 and p = 0.004, respectively). In healthy cats, the number of lavage neutrophils was higher when they received R,S- and S-albuterol compared with other treatments (p = 0.04). Conclusion: Airway inflammation is induced in both healthy and asthmatic cats with regular inhalation of racemic and S-albuterol, but not with R-albuterol.

β2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells

“…Application of (S)-albuterol and (S,S)-formoterol resulted in reduced Mp load only in normal cells, but not cells from asthmatics and COPD patients. (S)-albuterol has traditionally been thought to be inert, but studies have shown that the (S)-isomer may actually increase inflammation and negate the anti-inflammatory effects of (R)-albuterol[18,19]. It is therefore not surprising to observe differing antimicrobial effects of (S)- and (S,S)-isomers in cells from various study groups (e.g., normal subjects versus asthma and COPD patients).…”

“…Therefore, it is beneficial to enhance airway production of endogenous antimicrobial substances to promote the clearance of invading bacteria. In this study, we seek to identify a novel function of the short- and long-acting β2-agonists albuterol and formoterol, in (R)-, (R,R)-, racemic, (S)-, or (S,S)-isomeric forms, which have different efficacies in bronchodilation [18-20]. Specifically, we hypothesize that β2-agonists possess an antimicrobial function by decreasing bacterial levels in primary human bronchial epithelial cells from normal subjects, asthmatics, and COPD patients.…”

Respiratory and Thoracic Medicine

“…64,175 Terbutaline should be used with care in patients with preexisting cardiac disease, hyperthyroidism, hypertension, or seizures. 4,100,117,202,228 Chronic use of the inactive form can result in worsening airway inflammation in humans 100,117,202 and in cats. The drug is available in an MDI as salbutamol (100 µg/actuation) in most of the world and as albuterol (90 µg/actuation) in the United States.…”

“…Salbutamol (International Nonproprietary Name) and albuterol (United States Adopted Name) are different names for the same drug. 228 Where available, single enantiomer R-salbutamol or albuterol should be used. In humans salbutamol or albuterol results in significant bronchodilation within 5 to 15 minutes and lasts for 3 to 4 hours.…”

Simultaneous Estimation of Salbutamol, Oxtriphylline and Bromhexine Hydrochloride in Tablet Dosage Form by RP-HPLC

“…R-enantiomer has bronchodilatory and antiinflammatory effects and S-enantiomer is associated with increased airway hyper reactivity and pro-inflammatory effects [1]. The literature survey reveals that, salbutamol is reported in USP [2].…”