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Laboratory and Animal Investigations |

Is β-Adrenergic-Mediated Airway Relaxation of Salmeterol Antagonized by Its Solvent Xinafoic Acid?*

Harald Groeben, MD; Charles Emala, MD
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Affiliations: ,  *From Abteilung für Anaesthesiologie & Intensivmedizin (Dr. Groeben), Universität Essen, Germany; and the Department of Anesthesiology and Environmental Health Sciences (Dr. Emala), The Johns Hopkins Medical Institutions, Baltimore, MD.

Affiliations: ,  *From Abteilung für Anaesthesiologie & Intensivmedizin (Dr. Groeben), Universität Essen, Germany; and the Department of Anesthesiology and Environmental Health Sciences (Dr. Emala), The Johns Hopkins Medical Institutions, Baltimore, MD.



Chest. 1999;115(6):1678-1683. doi:10.1378/chest.115.6.1678
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Study objective: Isolated case reports of asthmatic fatalities accompanied by the use of salmeterol have raised the question whether a paradoxical effect of salmeterol or its vehicle on the airways might contribute to these fatalities. We questioned whether salmeterol′s solvent, xinafoic acid, has detrimental effects on the tone of airways or on β-adrenoceptor binding.

Materials and methods: Basenji-greyhound dogs were anesthetized and their peripheral airways challenged with xinafoic acid via a wedged bronchoscope technique. Radioligand binding assays were performed in lung membranes prepared from these dogs.

Results: In contrast to a methacholine control, xinafoic acid (0.001 to 1.0 mg/mL) aerosolized into the peripheral airways of anesthetized dogs did not increase airway resistance. Xinafoate alone had no significant effect on the specific binding of 125I-cyanopindolol to lung membranes and did not affect the affinity of salmeterol for theβ -adrenoceptor in the absence or presence of xinafoate, respectively (−log concentration that inhibits 50% [IC50] of the high-affinity site, 7.7 ± 0.15 and 7.9 ± 0.27; −log IC50 of the low-affinity site = 5.6 ± 0.44 and 5.3 ± 0.28 [n = 4]).

Conclusion: These findings suggest that xinafoic acid, the solvent for salmeterol, does not have direct airway irritant effects, does not bind to β-adrenoceptors, and does not impair the binding of salmeterol to β-adrenoceptors. Thus, xinafoate is unlikely to contribute to the worsening of airway symptoms in asthmatics using salmeterol xinafoate.

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