Dorzolamide

324.44

324.44

1533716-785-6

9JDX055TW1

DTXSID7022960

C62026

S - Sensory organs

-1

1.53±0.1 g/cm3

283-285°C

575.8±60.0 °C(Predicted)

6.99e-01 g/L

pKa 6.35 (Uncertain);8.50 (Uncertain)

3

36/37/38

26

XJ9095169

Xi

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.

Dorzolamide is approximately 33% bound to plasma proteins.

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.|FDA Label

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.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)|A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES. (See all compounds classified as Carbonic Anhydrase Inhibitors.)

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.|Dorzolamide is primarily excreted unchanged in the urine; however, N-desethyldorzolamide is also detected in the urine.|There is limited information on the volume of distribution of dorzolamide; however, the plasma concentrations of dorzolamide and its main metabolite are generally below the assay limit of quantitation, which is 15nM. Dorzolamide accumulates in red blood cells following chronic administration as a result of binding to CA-II, which is contained in peripheral red blood cells (RBCs).|There is limited information on the clearance rate of dorzolamide.

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.

As the drug administration is stopped, dorzolamide stored in RBCs is washed out of RBCs in a non-linear fashion, with the terminal elimination half-life of ≥120 days in RBCs. This initial rapid decline in drug concentrations is followed by the slow elimination phase, where the elimination half-life of the drug is about >4 months.

Elevated intraocular pressure is a characteristic manifestation of ocular hypertension or open-angle glaucoma. The level of intraocular pressure (IOP) is governed by the balance between the production of aqueous humour (by ocular ciliary processes) and its outflow from the anterior segment of the eye via trabecular (conventional) or uveoscleral (unconventional) pathways. When there is an increase in the resistance to the trabecular outflow of aqueous humour, the intraocular pressure is elevated. Subsequently, optic nerve damage can occur from blood flow restrictions and mechanical distortion of ocular structures. Optic nerve damage can further result in optic disc cupping and progressive visual field loss (and blindness in some cases). Carbonic anhydrase (CA) is a ubiquitous enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate ions and dehydration of carbonic acid. In the ocular ciliary processes, the local production of bicarbonate by CAs promotes sodium and fluid transport. CA-II is a key isoenzyme found primarily in red blood cells (RBCs) that regulates aqueous humour production. Dorzolamide is a highly specific CA-II inhibitor, where it displays a 4000-fold higher affinity for carbonic anhydrase II than carbonic anhydrase I. The inhibition of CA-II in the ciliary process disrupts the formation of bicarbonate ions and reduces sodium and fluid transport, which leads to decreased aqueous humour secretion and reduced intraocular pressure.

4-ethylamino-5,6-dihydro-6-methyl-7,7-dioxide-4H-thieno(2,3-b)thiopyran-2-sulfonamide

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