What separates XOPENEX Inhalation Solution from racemic albuterol and the rest…

XOPENEX contains only the (R)-isomer.

XOPENEX Inhalation Solution is indicated for the treatment or prevention of bronchospasm in patients 6 years of age or older with reversible obstructive airway disease.

Compare the preclinical characteristics of (R)- and (S)-albuterol*
*Clinical significance is unknown.

(S)-isomer:

• Very limited binding to the beta2-receptor^1,2
• Produces no bronchodilation³
• Diminishes the effects of steroids⁴
• Augments inflammatory stimuli^4-6

(R)-isomer:

• Potent binding to the beta2-receptor^1,2
• Produces all of the bronchodilation³
• Enhances the effects of steroids⁴
• Has no effect on or reduces inflammatory stimuli^4,5

Does the (R)-isomer need to be combined with the (S)-isomer?
No. The (R)-isomer is effective with or without the (S)-isomer and, in fact, is responsible for the clinical bronchodilation.  When racemic albuterol is inhaled and traverses the airway bronchioles, (R)-albuterol has a high affinity for and binds to the beta2-adrenergic receptors on the surface of bronchiolar smooth muscle cells. (R)-albuterol binding to these beta-receptors results in a conformational change in the receptor, thus inducing intracellular signaling. The complex cascade of signaling pathways causes activation of adenylate cyclase, increased cyclic AMP, and eventually activation of regulatory proteins. This in turn leads to a sequestering of calcium. The net effect is a decrease in intracellular calcium and ultimately smooth muscle relaxation, or bronchodilation. It is (R)-albuterol that produces all the bronchodilation.

XOPENEX INHALATION SOLUTION—A PROVEN PERFORMER

• Prescribed for millions of patients since 1999^7,8
• Approved for patients 6 years of age and older⁹

References:
1. Mitra S, Ugur M, Ugur O, et al. (S)-albuterol increases intracellular free calcium by muscarinic receptor activation and a phospholipase C-dependent mechanism in airway smooth muscle. Mol Pharmacol. 1998;53(3):347-354.
2. Penn RB, Frielle T, McCullough JR, et al. Comparison of R-, S-, and RS-albuterol interaction with human β1- and β2-adrenergic receptors. Clin Rev Allergy Immunol. 1996;14(1):37-45.
3. Lötvall J, Palmqvist M, Arvidsson P, et al. The therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients. J Allergy Clin Immunol. 2001;108(5):726-731.
4. Ameredes BT, Calhoun WJ. Modulation of GM-CSF release by enantiomers of beta-agonists in human airway smooth muscle. J Allergy Clin Immunol. 2005;116(1):65-72.
5. Agrawal DK, Ariyarathna K, Kelbe PW. (S)-albuterol activates pro-constrictory and pro-inflammatory pathways in human bronchial smooth muscle cells. J Allergy Clin Immunol. 2004;113(3):503-510.
6. Volcheck GW, Kelkar P, Bartemes KR, et al. Effects of (R)- and (S)-isomers of β-adrenergic agonists on eosinophil response to interleukin-5. Clin Exp Allergy. 2005;35(10): 1341-1346.
7. Verispan’s Physicians Drug & Diagnosis Audit, MAT, February 2006-March 2007.
8. IMS National Prescription Audit Plus, 1999-2007.

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