TEMPORAL VARIATION IN THE EFFECTS OF OPHTHALMIC TIMOLOL ON CARDIOVASCULAR AND RESPIRATORY FUNCTIONS IN HEALTHY-MEN

This study examined the effects of ophthalmic timolol and time of admi nistration on cardiovascular and respiratory functions in healthy youn g male volunteers. Eight participants (mean age +/- standard deviation , 22 +/- 0.9 years) received either 50 mu L of 0.5% timolol or placebo in the lower conjunctival sacs of both eyes in the morning or evening . Intraocular pressure, blood pressure, heart rate, and respiratory fu nctions, including percent forced expiratory volume in 1 second and pe ak expiratory flow rate, were then measured for 3 hours after drug adm inistration. Timolol reduced intraocular pressure and cardiovascular f unction at both administration times. However, a timolol-induced reduc tion in respiratory function was observed only in the evening: percent forced expiratory volume in 1 second, peak expiratory flow rate, and expiratory flow rate at 75% vital capacity were reduced by 3%, 7%, and 12%, respectively, 3 hours after administration. These results indica te that ophthalmic timolol reduces cardiovascular and respiratory func tions in healthy young male subjects and that bronchial sensitivity to timolol differs between morning and evening.