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.
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.
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.