Comparison of the airway response to eye drops of timolol and its isomer L‐714,465 in asthmatic subjects.

Abstract

1. The inadvertent administration of timolol to asthmatic patients continues to cause occasional severe and even fatal attacks of asthma. The (R)‐enantiomer of timolol, L‐714,465, is four times less potent than timolol in reducing intraocular pressure in man. It is 49 times less potent than timolol on beta 2‐adrenoceptors in animals and 13 times less potent on the airways of normal subjects. These findings suggested that L‐714,465 might be a safer alternative for the treatment of glaucoma. 2. Ten subjects with mild asthma who bronchoconstricted to timolol eye drops (0.25 or 0.5%) were studied. Airway dose‐response curves to timolol (0‐2%), L‐714,465 (0‐4%), and placebo (methyl cellulose) eye drops were performed in a double‐blind randomised study in which airway response was measured as change in FEV1 and specific airway conductance (sGaw). 3. L‐714,465 and timolol caused dose dependent falls in sGaw and FEV1 with L‐714,465 being approximately four times less potent than timolol. The geometric mean dose ratio was 3.89 for FEV1 (95% confidence interval (CI) 1.7‐8.7) and 3.93 (95% CI 2‐ 7.8) for sGaw. Since the difference in potency is similar to the reported difference in potency of the two drugs on intraocular pressure we conclude that L‐714,465 would not have a greater safety margin than timolol. 4. After completion of the dose‐response study eight subjects inhaled ipratropium bromide (72 micrograms) and this caused an increase in FEV1 from 74% to 80% of baseline.(ABSTRACT TRUNCATED AT 250 WORDS)