OCULAR PHARMACOKINETICS OF VERAPAMIL IN RABBITS

Previously, it had been demonstrated that cataract in diabetic rats ca n be prevented by systemical administration of the calcium channel blo cker verapamil. In addition to that, 0.125% verapamil eye drops were f ound to significantly reduce the intraocular pressure in ocular hypert ensive human subjects. The purpose of this study was to investigate th e ocular penetration and elimination of verapamil after topical admini stration of the drug in rabbits. Two drops of a 0.125% aqueous solutio n of RS-verapammil hydrochloride (corresponding to a total dose of 125 mu g RS-verapamil hydrochloride) were administered into the conjuncti val sac. Aqueous humor and blood samples were taken at different times after administration and analysed for drug concentration by combined gas chromatography-mass spectroscopy. Following the instillation of 0. 125% verapamil eye drops in a total dose of 125 mu g RS-verapamil, mea n (+/- SEM) aqueous humor peak levels of 1607 +/- 272 ng/ml were achie ved after 20 min. Mean half-life for the elimination from the aqueous humor was 33 min. Topical application of verapamil produced very low s erum peak concentrations (10.5 +/- 1.3 ng/ml). The results of our stud y demonstrate that topically administered verapamil readily penetrates into the anterior chamber leading to aqueous humor drug levels in the mu M range without producing serum levels that are high enough to cau se cardiovascular side effects.