Peringatan Keamanan

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.^L11386

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.^L11377

Dorzolamide

DB00869

small molecule approved

Deskripsi

Dorzolamide is a non-bacteriostatic sulfonamide derivative ^A1304 and topical carbonic anhydrase (CA) inhibitor that treats elevated intraocular pressure (IOP) associated with open-angle glaucoma and ocular hypertension.^L11377 It works by blocking an enzyme in the ciliary process that regulates ion balance and fluid pressure in the eyes.^A1303 Unlike oral CA inhibitors, dorzolamide has negligible effects of acid-base or electrolyte disturbances and other systemic adverse effects.^A1304 First marketed in 1995,^A190624 dorzolamide is available in ophthalmic solutions as monotherapy marketed as Trusopt ^L11377 or in combination with timolol as Cosopt PF.^L11380

Struktur Molekul 2D

Berat 324.44

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) As the drug administration is stopped, dorzolamide stored in RBCs is washed out of RBCs in a non-linear fashion,[L11377] with the terminal elimination half-life of ?120 days in RBCs.[A1304] 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.[A1303]

Volume Distribusi 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).[L11377]

Klirens (Clearance) There is limited information on the clearance rate of dorzolamide.

Absorpsi

Dorzolamide readily penetrated into the eye in animal studies.^A1304 Upon ophthalmic administration, dorzolamide is absorbed via the cornea and stroma.^A1303 Dorzolamide is reported to be absorbed systematically following topical administration.^L11377 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.^L11377

Metabolisme

Dorzolamide is slowly metabolised to N-desethyldorzolamide, which has a less potent pharmacological activity on CA-II and some inhibitory effect on CA-I.^L11377 Like the parent drug, N-desethyldorzolamide is also stored in RBCs, where it binds to CA-I.A1303,L11377 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.^A190552

Rute Eliminasi

Dorzolamide is primarily excreted unchanged in the urine; however, N-desethyldorzolamide is also detected in the urine.^L11377

Interaksi Obat

234 Data

Valsartan	Valsartan may increase the hypotensive activities of Dorzolamide.
Ramipril	Ramipril may increase the hypotensive activities of Dorzolamide.
Esmolol	Esmolol may increase the hypotensive activities of Dorzolamide.
Betaxolol	Betaxolol may increase the hypotensive activities of Dorzolamide.
Reserpine	Reserpine may increase the hypotensive activities of Dorzolamide.
Remikiren	Remikiren may increase the hypotensive activities of Dorzolamide.
Torasemide	Torasemide may increase the hypotensive activities of Dorzolamide.
Bethanidine	Bethanidine may increase the hypotensive activities of Dorzolamide.
Guanadrel	Guanadrel may increase the hypotensive activities of Dorzolamide.
Metoprolol	Metoprolol may increase the hypotensive activities of Dorzolamide.
Isradipine	Isradipine may increase the hypotensive activities of Dorzolamide.
Olmesartan	Olmesartan may increase the hypotensive activities of Dorzolamide.
Chlorthalidone	Chlorthalidone may increase the hypotensive activities of Dorzolamide.
Nitroprusside	Nitroprusside may increase the hypotensive activities of Dorzolamide.
Atenolol	Atenolol may increase the hypotensive activities of Dorzolamide.
Diltiazem	Diltiazem may increase the hypotensive activities of Dorzolamide.
Minoxidil	Minoxidil may increase the hypotensive activities of Dorzolamide.
Timolol	Timolol may increase the hypotensive activities of Dorzolamide.
Treprostinil	Treprostinil may increase the hypotensive activities of Dorzolamide.
Amlodipine	Amlodipine may increase the hypotensive activities of Dorzolamide.
Nimodipine	Nimodipine may increase the hypotensive activities of Dorzolamide.
Nisoldipine	Nisoldipine may increase the hypotensive activities of Dorzolamide.
Prazosin	Prazosin may increase the hypotensive activities of Dorzolamide.
Fosinopril	Fosinopril may increase the hypotensive activities of Dorzolamide.
Trandolapril	Trandolapril may increase the hypotensive activities of Dorzolamide.
Carteolol	Carteolol may increase the hypotensive activities of Dorzolamide.
Metolazone	Metolazone may increase the hypotensive activities of Dorzolamide.
Lercanidipine	Lercanidipine may increase the hypotensive activities of Dorzolamide.
Benazepril	Benazepril may increase the hypotensive activities of Dorzolamide.
Bosentan	Bosentan may increase the hypotensive activities of Dorzolamide.
Propranolol	Propranolol may increase the hypotensive activities of Dorzolamide.
Clonidine	Clonidine may increase the hypotensive activities of Dorzolamide.
Enalapril	Enalapril may increase the hypotensive activities of Dorzolamide.
Doxazosin	Doxazosin may increase the hypotensive activities of Dorzolamide.
Labetalol	Labetalol may increase the hypotensive activities of Dorzolamide.
Bisoprolol	Bisoprolol may increase the hypotensive activities of Dorzolamide.
Candoxatril	Candoxatril may increase the hypotensive activities of Dorzolamide.
Nicardipine	Nicardipine may increase the hypotensive activities of Dorzolamide.
Guanabenz	Guanabenz may increase the hypotensive activities of Dorzolamide.
Mecamylamine	Mecamylamine may increase the hypotensive activities of Dorzolamide.
Losartan	Losartan may increase the hypotensive activities of Dorzolamide.
Moexipril	Moexipril may increase the hypotensive activities of Dorzolamide.
Phentolamine	Phentolamine may increase the hypotensive activities of Dorzolamide.
Eplerenone	Eplerenone may increase the hypotensive activities of Dorzolamide.
Lisinopril	Lisinopril may increase the hypotensive activities of Dorzolamide.
Nitroglycerin	Nitroglycerin may increase the hypotensive activities of Dorzolamide.
Metyrosine	Metyrosine may increase the hypotensive activities of Dorzolamide.
Cryptenamine	Cryptenamine may increase the hypotensive activities of Dorzolamide.
Perindopril	Perindopril may increase the hypotensive activities of Dorzolamide.
Candesartan cilexetil	Candesartan cilexetil may increase the hypotensive activities of Dorzolamide.
Tolazoline	Tolazoline may increase the hypotensive activities of Dorzolamide.
Fenoldopam	Fenoldopam may increase the hypotensive activities of Dorzolamide.
Tadalafil	Tadalafil may increase the hypotensive activities of Dorzolamide.
Alprenolol	Alprenolol may increase the hypotensive activities of Dorzolamide.
Eprosartan	Dorzolamide may increase the hypotensive activities of Eprosartan.
Quinapril	Dorzolamide may increase the hypotensive activities of Quinapril.
Omapatrilat	Dorzolamide may increase the hypotensive activities of Omapatrilat.
Bimatoprost	Dorzolamide may increase the hypotensive activities of Bimatoprost.
Phenoxybenzamine	Dorzolamide may increase the hypotensive activities of Phenoxybenzamine.
Pindolol	Dorzolamide may increase the hypotensive activities of Pindolol.
Telmisartan	Dorzolamide may increase the hypotensive activities of Telmisartan.
Methyldopa	Dorzolamide may increase the hypotensive activities of Methyldopa.
Guanfacine	Dorzolamide may increase the hypotensive activities of Guanfacine.
Felodipine	Dorzolamide may increase the hypotensive activities of Felodipine.
Irbesartan	Dorzolamide may increase the hypotensive activities of Irbesartan.
Nitrendipine	Dorzolamide may increase the hypotensive activities of Nitrendipine.
Deserpidine	Dorzolamide may increase the hypotensive activities of Deserpidine.
Pentolinium	Dorzolamide may increase the hypotensive activities of Pentolinium.
Trimethaphan	Dorzolamide may increase the hypotensive activities of Trimethaphan.
Diazoxide	Dorzolamide may increase the hypotensive activities of Diazoxide.
Carvedilol	Dorzolamide may increase the hypotensive activities of Carvedilol.
Bretylium	Dorzolamide may increase the hypotensive activities of Bretylium.
Terazosin	Dorzolamide may increase the hypotensive activities of Terazosin.
Guanethidine	Dorzolamide may increase the hypotensive activities of Guanethidine.
Rescinnamine	Dorzolamide may increase the hypotensive activities of Rescinnamine.
Acebutolol	Dorzolamide may increase the hypotensive activities of Acebutolol.
Captopril	Dorzolamide may increase the hypotensive activities of Captopril.
Nadolol	Dorzolamide may increase the hypotensive activities of Nadolol.
Metipranolol	Dorzolamide may increase the hypotensive activities of Metipranolol.
Epoprostenol	Dorzolamide may increase the hypotensive activities of Epoprostenol.
Bepridil	Dorzolamide may increase the hypotensive activities of Bepridil.
Hydralazine	Dorzolamide may increase the hypotensive activities of Hydralazine.
Bevantolol	Dorzolamide may increase the hypotensive activities of Bevantolol.
Practolol	Dorzolamide may increase the hypotensive activities of Practolol.
Cilazapril	Dorzolamide may increase the hypotensive activities of Cilazapril.
Saprisartan	Dorzolamide may increase the hypotensive activities of Saprisartan.
Spirapril	Dorzolamide may increase the hypotensive activities of Spirapril.
Penbutolol	Dorzolamide may increase the hypotensive activities of Penbutolol.
Mibefradil	Dorzolamide may increase the hypotensive activities of Mibefradil.
Oxprenolol	Dorzolamide may increase the hypotensive activities of Oxprenolol.
Pargyline	Dorzolamide may increase the hypotensive activities of Pargyline.
Dexpropranolol	Dorzolamide may increase the hypotensive activities of Dexpropranolol.
Tienilic acid	Dorzolamide may increase the hypotensive activities of Tienilic acid.
Debrisoquine	Dorzolamide may increase the hypotensive activities of Debrisoquine.
Celiprolol	Dorzolamide may increase the hypotensive activities of Celiprolol.
Nebivolol	Dorzolamide may increase the hypotensive activities of Nebivolol.
Lofexidine	Dorzolamide may increase the hypotensive activities of Lofexidine.
Sitaxentan	Dorzolamide may increase the hypotensive activities of Sitaxentan.
Ambrisentan	Dorzolamide may increase the hypotensive activities of Ambrisentan.
Diethylnorspermine	Dorzolamide may increase the hypotensive activities of Diethylnorspermine.

Target Protein

Carbonic anhydrase 2 CA2

Carbonic anhydrase 4 CA4

Carbonic anhydrase 1 CA1

Carbonic anhydrase 3 CA3

Referensi & Sumber

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.

Artikel (PubMed)

PMID: 11929320
Martens-Lobenhoffer J, Banditt P: Clinical pharmacokinetics of dorzolamide. Clin Pharmacokinet. 2002;41(3):197-205.
PMID: 9143858
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.
PMID: 12658557
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.
PMID: 7895610
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.
PMID: 22269010
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.

Link

Contoh Produk & Brand

Produk: 113 • International brands: 0

Produk

Act Dorzotimolol

Solution • - • Ophthalmic • Canada • Approved
Ag-dorzolamide Timolol

Solution • - • Ophthalmic • Canada • Generic • Approved
Apo-dorzo-timop

Solution • - • Ophthalmic • Canada • Generic • Approved
Apo-dorzolamide

Solution • 2 % • Ophthalmic • Canada • Generic • Approved
Brim-Dor PF

Solution / drops • - • Ophthalmic • US
Cosopt

Solution • - • Ophthalmic • US • Approved
Cosopt

Solution • - • Ophthalmic • US • Approved
Cosopt

Solution / drops • - • Ophthalmic • US • Approved

Menampilkan 8 dari 113 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.