Identification

Name
Dorzolamide
Accession Number
DB00869  (APRD00577, DB04507)
Type
Small Molecule
Groups
Approved
Description

Dorzolamide is a non-bacteriostatic sulfonamide derivative 2 and topical carbonic anhydrase (CA) inhibitor that treats elevated intraocular pressure (IOP) associated with open-angle glaucoma and ocular hypertension.6 It works by blocking an enzyme in the ciliary process that regulates ion balance and fluid pressure in the eyes.1 Unlike oral CA inhibitors, dorzolamide has negligible effects of acid-base or electrolyte disturbances and other systemic adverse effects.2 First marketed in 1995,5 dorzolamide is available in ophthalmic solutions as monotherapy marketed as Trusopt 6 or in combination with timolol as Cosopt PF.7

Structure
Thumb
Synonyms
  • (4S,6S)-4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide
  • (4S,trans)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide
  • 4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide
  • 4-ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda6-thieno[2,3-b]thiopyran-2-sulfonic acid amide
  • 4S,6S-dorzolamide
  • Dorzolamid
  • Dorzolamida
  • Dorzolamide
  • Dorzolamidum
External IDs
L 671152 / MK 507
Product Ingredients
IngredientUNIICASInChI Key
Dorzolamide hydrochlorideQZO5366EW7130693-82-2OSRUSFPMRGDLAG-QMGYSKNISA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DorzolamideSolutionOphthalmicAlcon, Inc.Not applicableNot applicableCanada
Dorzolamide Eye Drops BPSolutionOphthalmicTeligent Canada IncNot applicableNot applicableCanada
Dorzolamide HydrochlorideSolution20 mg/1mLOphthalmicPrasco, Laboratories1994-12-092014-08-31Us
Dorzolamide Hydrochloride Ophthalmic SolutionSolution20 mgOphthalmicBausch & Lomb IncNot applicableNot applicableCanada
Dorzolamide PFSolution / drops20 mg/1mLOphthalmicImprimisRx NJ2018-01-01Not applicableUs
TrusoptSolution2 %OphthalmicPurdue Pharma2006-02-01Not applicableCanada
TrusoptSolution2 %OphthalmicPurdue Pharma1996-12-31Not applicableCanada
TrusoptSolution20 mg/1mLOphthalmicMerck Sharp & Dohme Corp.1994-12-09Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-dorzolamideSolutionOphthalmicApotex CorporationNot applicableNot applicableCanada
Dorzolamide HClSolution / drops20 mg/1mLOphthalmicA-S Medication Solutions2009-06-25Not applicableUs
Dorzolamide HClSolution20 mg/1mLOphthalmicActavis Pharma Company2015-02-172019-02-28Us
Dorzolamide HClSolution20 mg/1mLOphthalmicA-S Medication Solutions2015-02-17Not applicableUs
Dorzolamide HClSolution / drops20 mg/1mLOphthalmicBauch & Lomb Incorporated2009-06-25Not applicableUs
Dorzolamide HClSolution / drops22.3 mg/1mLOphthalmicPhysicians Total Care, Inc.2012-02-21Not applicableUs
Dorzolamide hydrochlorideSolution20 mg/1mLOphthalmicFdc Limited2019-11-16Not applicableUs
Dorzolamide HydrochlorideSolution / drops20 mg/1mLOphthalmicAlembic Pharmaceuticals Inc.2019-08-09Not applicableUs
Dorzolamide HydrochlorideSolution20 mg/1mLOphthalmicTeva Pharmaceuticals USA, Inc.2010-01-282019-05-31Us
Dorzolamide HydrochlorideSolution / drops20 mg/1mLOphthalmicRemedy Repack2013-11-182014-11-18Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Act DorzotimololDorzolamide (20 mg) + Timolol (5 mg)SolutionOphthalmicTEVA Canada Limited2013-05-01Not applicableCanada
Apo-dorzo-timopDorzolamide (20 mg) + Timolol (5 mg)SolutionOphthalmicApotex Corporation2010-12-15Not applicableCanada
CosoptDorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicAkorn2014-04-30Not applicableUs
CosoptDorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)SolutionOphthalmicMerck Sharp & Dohme Limited1998-04-072015-12-31Us
CosoptDorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)SolutionOphthalmicPhysicians Total Care, Inc.2002-10-29Not applicableUs
CosoptDorzolamide (20 mg) + Timolol (5 mg)SolutionOphthalmicPurdue Pharma2005-11-02Not applicableCanada
CosoptDorzolamide (20 mg) + Timolol (5 mg)SolutionOphthalmicPurdue Pharma1999-05-27Not applicableCanada
Cosopt PFDorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)SolutionOphthalmicMerck Sharp & Dohme Limited2012-02-012016-03-31Us
Cosopt PFDorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicAkorn2014-05-14Not applicableUs
Dorzolamide and TimololDorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)SolutionOphthalmicFdc Limited2019-11-16Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Brim-Dor PFDorzolamide hydrochloride (20 mg/1mL) + Brimonidine tartrate (1.5 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Dorzolamide PFDorzolamide hydrochloride (20 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Brim-Dor PFDorzolamide hydrochloride (20 mg/1mL) + Brimonidine tartrate (1.5 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Brim-Dor-LatDorzolamide hydrochloride (20 mg/1mL) + Brimonidine tartrate (1.5 mg/1mL) + Latanoprost (0.05 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Dor PFDorzolamide hydrochloride (20 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Tim-Dor-LatDorzolamide hydrochloride (20 mg/1mL) + Latanoprost (0.05 mg/1mL) + Timolol maleate (5 mg/1mL)Solution / dropsOphthalmicImprimisRx NJ2018-01-01Not applicableUs
Categories
UNII
9JDX055TW1
CAS number
120279-96-1
Weight
Average: 324.44
Monoisotopic: 324.02721908
Chemical Formula
C10H16N2O4S3
InChI Key
IAVUPMFITXYVAF-XPUUQOCRSA-N
InChI
InChI=1S/C10H16N2O4S3/c1-3-12-8-4-6(2)18(13,14)10-7(8)5-9(17-10)19(11,15)16/h5-6,8,12H,3-4H2,1-2H3,(H2,11,15,16)/t6-,8-/m0/s1
IUPAC Name
(2S,4S)-4-(ethylamino)-2-methyl-1,1-dioxo-2H,3H,4H-1λ⁶-thieno[2,3-b]thiopyran-6-sulfonamide
SMILES
CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O

Pharmacology

Indication

Dorzolamide is indicated for the management of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.6 It can also be used in combination with timolol for the same indication in patients who are insufficiently responsive to ophthalmic beta-blockers.7

Its pre-operative use was also investigated to prevent elevated intraocular pressure after neodynium yttrium aluminum garnet laser posterior capsulotomy.3

Associated Conditions
Pharmacodynamics

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.2

Mechanism of action

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).2

Carbonic anhydrase (CA) is a ubiquitous enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate ions and dehydration of carbonic acid.2,6 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.2 Dorzolamide is a highly specific CA-II inhibitor, where it displays a 4000-fold higher affinity for carbonic anhydrase II than carbonic anhydrase I.2 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.2,6

TargetActionsOrganism
ACarbonic anhydrase 2
inhibitor
Humans
ACarbonic anhydrase 4
inhibitor
Humans
ACarbonic anhydrase 1
inhibitor
Humans
UCarbonic anhydrase 3
inhibitor
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

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Absorption

Dorzolamide readily penetrated into the eye in animal studies.2 Upon ophthalmic administration, dorzolamide is absorbed via the cornea and stroma.1 Dorzolamide is reported to be absorbed systematically following topical administration.6 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.6

Volume of distribution

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).6

Protein binding

Dorzolamide is approximately 33% bound to plasma proteins.6

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.6 Like the parent drug, N-desethyldorzolamide is also stored in RBCs, where it binds to CA-I.1,6 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.4

Route of elimination

Dorzolamide is primarily excreted unchanged in the urine; however, N-desethyldorzolamide is also detected in the urine.6

Half life

As the drug administration is stopped, dorzolamide stored in RBCs is washed out of RBCs in a non-linear fashion,6 with the terminal elimination half-life of ≥120 days in RBCs.2 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.1

Clearance

There is limited information on the clearance rate of dorzolamide.

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.8

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.6

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololDorzolamide may increase the hypotensive activities of Acebutolol.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Dorzolamide.
Acetylsalicylic acidThe risk or severity of metabolic acidosis can be increased when Dorzolamide is combined with Acetylsalicylic acid.
AliskirenDorzolamide may increase the hypotensive activities of Aliskiren.
AloxiprinThe risk or severity of metabolic acidosis can be increased when Dorzolamide is combined with Aloxiprin.
AlprenololAlprenolol may increase the hypotensive activities of Dorzolamide.
AmbrisentanDorzolamide may increase the hypotensive activities of Ambrisentan.
Aminosalicylic acidThe risk or severity of metabolic acidosis can be increased when Dorzolamide is combined with Aminosalicylic acid.
AmlodipineAmlodipine may increase the hypotensive activities of Dorzolamide.
Angiotensin 1-7Dorzolamide may increase the hypotensive activities of Angiotensin 1-7.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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    Action

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Food Interactions
No interactions found.

References

Synthesis Reference

Laszlo Kovacs, Csaba Szabo, Erika Molnarne, Adrienne Kovacsne-Mezei, Claude Singer, Judith Aronhime, "Method of making dorzolamide hydrochloride." U.S. Patent US20060155132, issued July 13, 2006.

US20060155132
General References
  1. Martens-Lobenhoffer J, Banditt P: Clinical pharmacokinetics of dorzolamide. Clin Pharmacokinet. 2002;41(3):197-205. [PubMed:11929320]
  2. Balfour JA, Wilde MI: Dorzolamide. A review of its pharmacology and therapeutic potential in the management of glaucoma and ocular hypertension. Drugs Aging. 1997 May;10(5):384-403. [PubMed:9143858]
  3. Arieta C, Amaral M, Matuda E, Crosta C, de Carvalho Moreira Filho D, Jose N: Dorzolamide X apraclonidine in the prevention of the intraocular pressure spike after Nd : YAG laser posterior capsulotomy. Curr Eye Res. 2002 Oct;25(4):237-41. doi: 10.1076/ceyr.25.4.237.13484. [PubMed:12658557]
  4. Hasegawa T, Hara K, Kenmochi T, Hata S: In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Drug Metab Dispos. 1994 Nov-Dec;22(6):916-21. [PubMed:7895610]
  5. Loftsson T, Jansook P, Stefansson E: Topical drug delivery to the eye: dorzolamide. Acta Ophthalmol. 2012 Nov;90(7):603-8. doi: 10.1111/j.1755-3768.2011.02299.x. Epub 2012 Jan 23. [PubMed:22269010]
  6. FDA Approved Drug Products: TRUSOPT (dorzolamide hydrochloride) ophthalmic solution [Link]
  7. FDA Approved Drug Products: COSOPT PF (dorzolamide hydrochloride, timolol maleate) ophthalmic solution [Link]
  8. Cayman Chemical Safety Data Sheet: Dorzolamide (hydrochloride) [Link]
External Links
Human Metabolome Database
HMDB0015007
KEGG Drug
D07871
KEGG Compound
C06969
PubChem Compound
5284549
PubChem Substance
46506754
ChemSpider
4447604
BindingDB
10884
RxNav
60207
ChEBI
4702
ChEMBL
CHEMBL218490
ZINC
ZINC000001530621
Therapeutic Targets Database
DAP000775
PharmGKB
PA164748765
PDBe Ligand
ETS
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dorzolamide
ATC Codes
S01EC03 — Dorzolamide
AHFS Codes
  • 52:40.12 — Carbonic Anhydrase Inhibitors
PDB Entries
1cil / 3fw3 / 4k13 / 4m2u / 4m2w / 6bc9
FDA label
Download (569 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentEye Diseases / Glaucoma / Ocular Hypertension1
1CompletedTreatmentGlaucoma1
1RecruitingTreatmentGlaucoma1
2CompletedTreatmentAge-Related Macular Degeneration (ARMD) / Diabetic Macular Edema (DME) / Retinal Vein Occlusion / Wet Macular Degeneration1
2CompletedTreatmentChildhood Glaucoma1
2CompletedTreatmentGlaucoma2
2CompletedTreatmentGlaucoma, Primary Open Angle (POAG)1
2CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
2Unknown StatusTreatmentHypertensive Phase1
2, 3CompletedBasic ScienceOpen-angle Glaucoma (OAG)1
2, 3RecruitingTreatmentNeovascular Age-Related Macular Degeneration / Wet Macular Degeneration1
3CompletedTreatmentGlaucoma1
3CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
3CompletedTreatmentGlaucoma / Ocular Hypertension4
3CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG) / Open-angle Glaucoma (OAG)1
3CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
3RecruitingPreventionGlaucoma1
3RecruitingTreatmentGlaucoma, Primary Open Angle (POAG)1
3TerminatedTreatmentGlaucoma / Ocular Hypertension1
3WithdrawnTreatmentGlaucoma / Ocular Hypertension1
4CompletedNot AvailableGlaucoma1
4CompletedNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)1
4CompletedBasic ScienceGlaucoma1
4CompletedOtherEye Disease1
4CompletedTreatmentExfoliation Syndrome / Ocular Hypertension / Open-angle Glaucoma (OAG) / Pigmentary Glaucoma1
4CompletedTreatmentGlaucoma5
4CompletedTreatmentGlaucoma, Primary Open Angle (POAG) / Ocular Hypertension1
4CompletedTreatmentGlaucoma / Ocular Hypertension3
4CompletedTreatmentGlaucoma / Ocular Surface Disease1
4CompletedTreatmentOcular Hypertension1
4CompletedTreatmentOcular Hypertension / Open Angle Glaucoma (OAG) / Open-angle Glaucoma (OAG)2
4CompletedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)5
4CompletedTreatmentOpen-angle Glaucoma (OAG)3
4RecruitingTreatmentGlaucoma1
4TerminatedTreatmentOcular Hypertension / Open-angle Glaucoma (OAG)1
4Unknown StatusBasic ScienceOpen Angle Glaucoma (OAG) / Open-angle Glaucoma (OAG)1
4Unknown StatusTreatmentGlaucoma1
4Unknown StatusTreatmentRetinal Degenerations1
Not AvailableCompletedNot AvailableGlaucoma1
Not AvailableCompletedNot AvailableGlaucoma Due to Silicon Oil / Rhegmatogenous Retinal Detachments / Toxic Effect of Silicone1
Not AvailableCompletedNot AvailableX-linked Retinoschisis / XLRS1
Not AvailableCompletedBasic ScienceDrug Effect (Glaucoma Drugs)1
Not AvailableCompletedBasic ScienceGlaucoma1
Not AvailableCompletedPreventionDiabetic Retinopathy (DR)1
Not AvailableCompletedTreatmentMacular Hole / Retinal Detachment1
Not AvailableCompletedTreatmentNormal Tension Glaucoma1
Not AvailableCompletedTreatmentScleral Buckling1
Not AvailableRecruitingNot AvailableDiabetic Macular Edema (DME) / Diabetic Retinopathy (DR)1
Not AvailableUnknown StatusDiagnosticGlaucoma1
Not AvailableUnknown StatusHealth Services ResearchOpen Angle Glaucoma (OAG) / Open-angle Glaucoma (OAG)1
Not AvailableUnknown StatusTreatmentExfoliation Syndrome / Glaucoma / Ocular Hypertension1
Not AvailableWithdrawnNot AvailableOcular Hypertension / Open-angle Glaucoma (OAG)1
Not AvailableWithdrawnBasic ScienceGlaucoma1

Pharmacoeconomics

Manufacturers
  • Alcon inc
  • Apotex inc
  • Bausch and lomb inc
  • Hi tech pharmacal co inc
  • Pharmaforce inc
  • Sandoz canada inc
  • Teva pharmaceuticals usa
  • Merck research laboratories div merck co inc
Packagers
  • Apotex Inc.
  • Dispensing Solutions
  • Falcon Pharmaceuticals Ltd.
  • Hi Tech Pharmacal Co. Inc.
  • Lake Erie Medical and Surgical Supply
  • Merck & Co.
  • Physicians Total Care Inc.
  • Prasco Labs
  • Sandoz
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
SolutionOphthalmic
SolutionOphthalmic
Solution / dropsOphthalmic20 mg/1mL
Solution / dropsOphthalmic22.3 mg/1mL
SolutionOphthalmic20 mg/1mL
Solution / dropsOphthalmic
SolutionOphthalmic20 mg
SolutionOphthalmic22.3 mg/1mL
SolutionOphthalmic2 %
Prices
Unit descriptionCostUnit
Trusopt 2% Solution 10ml79.25USD bottle
Dorzolamide HCl 2% Solution 10ml Bottle69.42USD bottle
Dorzolamide hcl 2% eye drops6.86USD ml
Trusopt 2% eye drops6.73USD ml
Trusopt (Preservative-Free) 2 % Solution3.93USD ml
Trusopt 2 % Solution3.93USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1329211No1994-05-032011-05-03Canada
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)264FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.699 mg/mLALOGPS
logP-0.5ALOGPS
logP-0.15ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)8.18ChemAxon
pKa (Strongest Basic)7.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area106.33 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity72.46 m3·mol-1ChemAxon
Polarizability31.55 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9944
Blood Brain Barrier+0.6697
Caco-2 permeable-0.6627
P-glycoprotein substrateSubstrate0.5389
P-glycoprotein inhibitor INon-inhibitor0.8855
P-glycoprotein inhibitor IINon-inhibitor0.8398
Renal organic cation transporterNon-inhibitor0.9011
CYP450 2C9 substrateNon-substrate0.7755
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5096
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7547
Ames testNon AMES toxic0.6397
CarcinogenicityNon-carcinogens0.6933
BiodegradationNot ready biodegradable0.9946
Rat acute toxicity2.2365 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9446
hERG inhibition (predictor II)Non-inhibitor0.8706
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 2,3,5-trisubstituted thiophenes. These are organic compounds containing a thiophene that is trisubstituted at the C-2, C3- and C5-positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Thiophenes
Sub Class
2,3,5-trisubstituted thiophenes
Direct Parent
2,3,5-trisubstituted thiophenes
Alternative Parents
Aralkylamines / Thiopyrans / Organosulfonamides / Sulfones / Heteroaromatic compounds / Aminosulfonyl compounds / Dialkylamines / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
2,3,5-trisubstituted thiophene / Aralkylamine / Organosulfonic acid amide / Thiopyran / Sulfone / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Aminosulfonyl compound / Heteroaromatic compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfonamide, thiophenes (CHEBI:4702)

Targets

Details
1. Carbonic anhydrase 2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
Molecular Weight
29245.895 Da
References
  1. Lachmann C, Jorg KM, Trinkmann R: [Postoperative behavior of intraocular pressure after posterior Nd:YAG laser capsulotomy--critical evaluation in preventive administration of local carbonic anhydrase II inhibitor dorzolamide hydrochloride (Trusopt)]. Klin Monbl Augenheilkd. 1998 Dec;213(6):326-30. [PubMed:10048009]
  2. Wong BK, Bruhin PJ, Barrish A, Lin JH: Nonlinear dorzolamide pharmacokinetics in rats: concentration-dependent erythrocyte distribution and drug-metabolite displacement interaction. Drug Metab Dispos. 1996 Jun;24(6):659-63. [PubMed:8781782]
  3. Berg JT, Ramanathan S, Gabrielli MG, Swenson ER: Carbonic anhydrase in mammalian vascular smooth muscle. J Histochem Cytochem. 2004 Aug;52(8):1101-6. [PubMed:15258186]
  4. Hasegawa T, Hara K, Hata S: Binding of dorzolamide and its metabolite, N-deethylated dorzolamide, to human erythrocytes in vitro. Drug Metab Dispos. 1994 May-Jun;22(3):377-82. [PubMed:8070313]
  5. Maren TH, Conroy CW, Wynns GC, Levy NS: Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1997 Feb;13(1):23-30. [PubMed:9029437]
  6. Sugrue MF: Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors. Prog Retin Eye Res. 2000 Jan;19(1):87-112. [PubMed:10614682]
  7. Sugrue MF: The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1996 Fall;12(3):363-76. [PubMed:8875343]
  8. Srinivas SP, Ong A, Zhai CB, Bonanno JA: Inhibition of carbonic anhydrase activity in cultured bovine corneal endothelial cells by dorzolamide. Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3273-8. [PubMed:12356834]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Details
2. Carbonic anhydrase 4
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina an...
Gene Name
CA4
Uniprot ID
P22748
Uniprot Name
Carbonic anhydrase 4
Molecular Weight
35032.075 Da
References
  1. Sugrue MF: The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1996 Fall;12(3):363-76. [PubMed:8875343]
Details
3. Carbonic anhydrase 1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
In vitro, dorzolamide is a much weaker inhibitor of human carbonic anhydrase isoenzyme I (IC50 value of 600 nM).
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name
CA1
Uniprot ID
P00915
Uniprot Name
Carbonic anhydrase 1
Molecular Weight
28870.0 Da
References
  1. Hasegawa T, Hara K, Hata S: Binding of dorzolamide and its metabolite, N-deethylated dorzolamide, to human erythrocytes in vitro. Drug Metab Dispos. 1994 May-Jun;22(3):377-82. [PubMed:8070313]
  2. Maren TH, Conroy CW, Wynns GC, Levy NS: Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1997 Feb;13(1):23-30. [PubMed:9029437]
  3. Sugrue MF: The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1996 Fall;12(3):363-76. [PubMed:8875343]
Details
4. Carbonic anhydrase 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide.
Gene Name
CA3
Uniprot ID
P07451
Uniprot Name
Carbonic anhydrase 3
Molecular Weight
29557.215 Da
References
  1. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [PubMed:17826101]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
Curator comments
An in vitro study using liver microsomes from Sprague-Dawley rats suggest the involvement of this enzyme in the metabolism of dorzolamide. It is unclear whether this drug-enzyme interaction can be expected with human liver enzymes.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
Cyp2b1
Uniprot ID
P00176
Uniprot Name
Cytochrome P450 2B1
Molecular Weight
55933.06 Da
References
  1. Hasegawa T, Hara K, Kenmochi T, Hata S: In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Drug Metab Dispos. 1994 Nov-Dec;22(6):916-21. [PubMed:7895610]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
An in vitro study using liver microsomes from Sprague-Dawley rats suggest the involvement of this enzyme in the metabolism of dorzolamide. It is unclear whether this drug-enzyme interaction can be expected with human liver enzymes.
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Hasegawa T, Hara K, Kenmochi T, Hata S: In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Drug Metab Dispos. 1994 Nov-Dec;22(6):916-21. [PubMed:7895610]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
Curator comments
An in vitro study using liver microsomes from Sprague-Dawley rats suggest the involvement of this enzyme in the metabolism of dorzolamide. It is unclear whether this drug-enzyme interaction can be expected with human liver enzymes.
General Function
Testosterone 6-beta-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
Cyp3a2
Uniprot ID
P05183
Uniprot Name
Cytochrome P450 3A2
Molecular Weight
57731.215 Da
References
  1. Hasegawa T, Hara K, Kenmochi T, Hata S: In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Drug Metab Dispos. 1994 Nov-Dec;22(6):916-21. [PubMed:7895610]

Drug created on June 13, 2005 07:24 / Updated on April 06, 2020 19:07

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