Dynamics and kinetics of ophthalmic timolol

Abstract

Timolol [TM] is a .beta. adrenergic antagonist in 0.25 or 0.5% eyedrop solution for glaucoma. In a double-blind crossover study in healthy males systemic .beta. blockade, intraocular pressure and TM kinetics were measured after the 1st and 9th 12 hourly doses of a 0.5% ophthalmic solution. TM ophthalmic and placebo were each given as 2 drops to each eye with precautions to prevent the normal loss of drug in tears and overflow (high dose) and as 1 drop to each eye with no special precautions (standard therapeutic dose). Exercise tachycardia, measured at 70 and 255 min after administration of drug, was lower at both levels. Postexercise 1 s forced expiratory volume was not affected. Intraocular pressure measured at 3 and 8 h after drug was lower at both dose levels. TM was consistently present in urine but was not detectable in most plasma samples. Dynamic effects were not greater after the 9th than after the 1st dose, and the urinary excretion data provided no evidence of drug cumulation.