Population pharmacokinetics of 2% topical dorzolamide in the aqueous humorof humans

PURPOSE. To evaluate the concentration and kinetics of dorzolamide in the a queous humor after its topical application. METHODS. Samples of aqueous humor were collected at the beginning of routin e cataract surgery at defined intervals after topical application of a 2% s olution of dorzolamide. After deep-frozen storage of the samples, drug extr action was achieved with a mixture of solvents. Quantification was carried out by high-performance liquid chromatography on a reversed-phase column. RESULTS. Peak concentrations of dorzolamide in aqueous humor were reached a pproximately 2 boors after application with 1000 ng/ml. Average values were approximately 1000 to 700 ng/ml after 4 to 6 hours and approximately 200 n g/ml after 12 hours. Mean half-life of absorption was 1.2 hours and for eli mination 3.0 hours. CONCLUSIONS. Pharmacokinetics of dorzolamide in the aqueous humor of humans are in comparable dimensions as previously reported in experimental trials in pigmented rabbits. There is a clear linear absorption and elimination k inetic, which is demonstrated using the Bateman function. It better knowled ge of the distribution and kinetics of dorzolamide will help to explain its reported effects on intraocular hemodynamics, distinct from its intraocula r pressure lowering effect.