Distribution of Verapamil and Norverapamil in the Eye and Systemic Circulation After Topical Administration of Verapamil in Rabbits

ABSTRACT Our purpose was to determine the pharmacokinetics of verapamil and its active metabolite norverapamil after topical administration of verapamil in rabbits. New Zealand white albino rabbits were given 50 μl of verapamil ophthalmic formulation topically in each eye. Samples obtained at various time points were analyzed with high performance liquid chromatography and tandem mass spectrometry. The elimination half-life of verapamil after treatment with 0.5% verapamil was 0.76 hour for aqueous, 4.34 hours for vitreous, and 1.82 hours for serum. The peak concentrations for aqueous, vitreous, and serum were 2.34 × 10−6 M by 0.5 hour, 1.57 × 10−7 M at 2 hours, and 3.39 × 10−8 M by 0.5 hour following instillation of one drop of 0.5% verapamil; and 1.41 × 10−6 M by 0.5 hour, 5.48 × 10−8 M at 4 hours, and 1.20 × 10−8 M by 0.5 hour following 0.25% verapamil, respectively. The metabolite norverapamil was found at peak concentrations of 8.65 × 10−8 M by 0.5 hour in aqueous, 1.65 × 10−8 M at 2 hours in vitreous...