Dorzolamide

Absorption

Dorzolamide readily penetrated into the eye in animal studies. Upon ophthalmic administration, dorzolamide is absorbed via the cornea and stroma. Dorzolamide is reported to be absorbed systematically following topical administration. The systemic exposure of dorzolamide following long-term administration was assessed in healthy subjects receiving an oral dose of 2 mg dorzolamide twice daily, which equates to the ophthalmic dose of 2% dorzolamide three times daily. In these subjects receiving the treatment for 20 weeks, the steady-state was reached within 8 weeks.

Toxicity

The oral LD50 of dorzolamide is 1927 mg/kg in rats and 1320 mg/kg in mice. The subcutaneous LD50 is >2 g/kg in both rats and mice.
Overdose may result in electrolyte imbalance, acidosis, and possibly central nervous system effects; these symptoms should be responded with appropriate supportive treatment. It is advised that the patient's serum electrolyte (particularly potassium) levels and blood pH levels are monitored in the case of a suspected overdose.

The Uses of Dorzolamide

Dorzolamide is an intermediate in synthesizing N-Acetyl Dorzolamide (A173640), a useful synthetic compound.

The Uses of Dorzolamide

Carbonic anhydrase inhibitor.

Background

Dorzolamide is a non-bacteriostatic sulfonamide derivative and topical carbonic anhydrase (CA) inhibitor that treats elevated intraocular pressure (IOP) associated with open-angle glaucoma and ocular hypertension. It works by blocking an enzyme in the ciliary process that regulates ion balance and fluid pressure in the eyes. Unlike oral CA inhibitors, dorzolamide has negligible effects of acid-base or electrolyte disturbances and other systemic adverse effects. First marketed in 1995, dorzolamide is available in ophthalmic solutions as monotherapy marketed as Trusopt or in combination with timolol as Cosopt PF.

Indications

Dorzolamide is indicated for the management of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. It can also be used in combination with timolol for the same indication in patients who are insufficiently responsive to ophthalmic beta-blockers.
Its pre-operative use was also investigated to prevent elevated intraocular pressure after neodynium yttrium aluminum garnet laser posterior capsulotomy.

Definition

ChEBI: 5,6-Dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide in which hydrogens at the 4 and 6 positions are substituted by ethylamino and methyl groups, respectively (4S, trans-configuration . A carbonic anhydrase inhibitor, it is used as the hydrochloride in ophthalmic solutions to lower increased intraocular pressure in the treatment of open-angle glaucoma and ocular hypertension.

brand name

Trusopt (Merck).

Pharmacokinetics

Dorzolamide is a carbonic anhydrase inhibitor that reduces elevated intraocular pressure in open-angle glaucoma or ocular hypertension. When used in combination with topic beta-adrenergic antagonists, dorzolamide has an additive effect of lowering intraocular pressure. The peak ocular hypotensive effect of dorzolamide is observed at about 2 hours following ophthalmic administration.

Metabolism

Dorzolamide is slowly metabolised to N-desethyldorzolamide, which has a less potent pharmacological activity on CA-II and some inhibitory effect on CA-I. Like the parent drug, N-desethyldorzolamide is also stored in RBCs, where it binds to CA-I. The findings of an in vitro study using liver microsomes from Sprague-Dawley rats suggest the involvement of CYP2B1, CYP2E1, and CYP3A2 in the metabolism of dorzolamide in rat liver.