Clinical pharmacokinetics of dorzolamide.
Dorzolamide is a carbonic anhydrase inhibitor for topical ophthalmic application. It is used in the treatment of glaucoma to lower the intraocular pressure. After absorption via the cornea and stroma, it inhibits carbonic anhydrase in the ciliary process, which leads to a reduction of aqueous humour production and therefore to the desired therapeutic effect. In the systemic circulation, dorzolamide is bound mainly to carbonic anhydrase in red blood cells. It is slowly metabolised to N-de-ethyldorzolamide, which in turn is also stored in red blood cells. The very slow elimination (half-life >4 months) of both substances takes place via the renal route. However, the inhibition of carbonic anhydrase in red blood cells is moderate in the course of a topical treatment, avoiding systemic adverse effects. This review summarises the pharmacokinetic and pharmacodynamic properties of dorzolamide and its metabolite in eye tissues and in the systemic circulation.
Martens-Lobenhoffer
Jens
J
Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany. Jens.Martens-Lobenhoffer@medizin.uni-magdeburg.de
Banditt
Peter
P
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002924:Ciliary Body / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007527:Isoenzymes; D009883:Ophthalmic Solutions; D013449:Sulfonamides / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D013876:Thiophenes / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology
D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; C062765:dorzolamide; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases; C456780:N-deethyldorzolamide