Respiratory and cardiovascular effects of WP-934 in guinea pigs

WP-934 is a newly developed reversible thermo-setting in situ gelling ophth almic solution containing timolol. We investigated the effects of WP-934 on the respiratory and cardiovascular systems in guinea pigs and compared the m with those of the conventional ophthalmic solution of timolol. At 30 min after instillation of timolol 0.5%, the airway responsiveness to histamine was 4 times higher, and that to acetylcholine was 2.5 times higher, than th at before instillation. At 30 min after instillation of WP-934 0.5%, in con trast, the increase in responsiveness to each drug was about half that seen with the conventional solution. Topical instillation of timolol 0.5% weake ned the effects of salbutamol and aminophylline on bronchodilatation, while that of WP-934 0.5% had no effect on aminophylline-induced bronchodilatati on and a weaker effect on salbutamol-induced bronchodiiatation. Topical ins tillation of timolol 0.5% and WP-934 0.5% failed to show a significant effe ct on blood pressure but caused a 10 to 20% decrease in heart rate for at l east 120 min after instillation. WP-934 appears to have less respiratory adverse effects than timolol, mainl y due to its longer retention on the ocular surface and a consequent decrea se in systemic absorption.