Population pharmacokinetics of 2% topical dorzolamide in the aqueous humor of humans.
OBJECTIVE
To evaluate the concentration and kinetics of dorzolamide in the aqueous humor after its topical application.


METHODS
Samples of aqueous humor were collected at the beginning of routine cataract surgery at defined intervals after topical application of a 2% solution of dorzolamide. After deep-frozen storage of the samples, drug extraction 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 approximately 2 hours after application with 1000 ng/ml. Average values were approximately 1000 to 700 ng/ml after 4 to 6 hours and approximately 200 ng/ml after 12 hours. Mean half-life of absorption was 1.2 hours and for elimination 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 kinetic, which is demonstrated using the Bateman function. A better knowledge of the distribution and kinetics of dorzolamide will help to explain its reported effects on intraocular hemodynamics, distinct from its intraocular pressure lowering effect.
Schmitz
K
K
Eye Department, Otto-von-Guericke-University, Magdeburg, Germany.
Banditt
P
P
Motschmann
M
M
Meyer
F P
FP
Behrens-Baumann
W
W
D000042:Absorption; D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000493:pharmacokinetics*; D002387:Cataract Extraction; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000493:pharmacokinetics*
D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; C062765:dorzolamide