Comparison of the airway response to eye drops of timolol and its isomer L-714,465 in asthmatic subjects.
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)
D000293:Adolescent; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005541:Forced Expiratory Volume; D006801:Humans; D009241:Ipratropium; D007536:Isomerism; D008875:Middle Aged; D009883:Ophthalmic Solutions; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology*
D009883:Ophthalmic Solutions; D013999:Timolol; D009241:Ipratropium; D000420:Albuterol