Hydrochlorothiazide
Explore a selection of our essential drug information below, or:
Identification
- Summary
Hydrochlorothiazide is a thiazide diuretic used to treat edema associated with a number of conditions, and hypertension.
- Brand Names
- Accuretic, Actelsar Hct, Aldactazide, Altace HCT, Atacand, Atacand Hct, Avalide, Benicar Hct, Diovan Hct, Exforge Hct, Hyzaar, Ifirmacombi, Karvezide, Lopressor Hct, Lotensin Hct, Micardis-hct, Olmetec Plus, Tekturna Hct, Teveten HCT, Tribenzor, Urozide, Vaseretic, Viskazide, Zestoretic, Ziac
- Generic Name
- Hydrochlorothiazide
- DrugBank Accession Number
- DB00999
- Background
Hydrochlorothiazide is the most commonly prescribed thiazide diuretic.2 It is indicated to treat edema and hypertension.2,10,11 Hydrochlorothiazide use is common but declining in favour of angiotensin converting enzyme inhibitors.2 Many combination products are available containing hydrochlorothiazide and angiotensin converting enzyme inhibitors14,15 or angiotensin II receptor blockers.12,13
Hydrochlorothiazide was granted FDA approval on 12 February 1959.9
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Structure
- Weight
- Average: 297.739
Monoisotopic: 296.964474846 - Chemical Formula
- C7H8ClN3O4S2
- Synonyms
- HCTZ
- Hidroclorotiazida
- Hydrochlorothiazide
- Hydrochlorothiazidum
- External IDs
- NSC-53477
- SU-5879
Pharmacology
- Indication
Hydrochlorothiazide is indicated alone or in combination for the management of edema associated with congestive heart failure, hepatic cirrhosis, nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and corticosteroid and estrogen therapy.10,11 Hydrochlorothiazide is also indicated alone or in combination for the management of hypertension.2,10,11,16
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Calcium nephrolithiasis ••• ••••• Used as adjunct in combination to manage Cirrhosis of liver Combination Product in combination with: Spironolactone (DB00421) •••••••••••• Used in combination to manage Congestive heart failure Combination Product in combination with: Spironolactone (DB00421), Digitoxin (DB01396) •••••••••••• Management of Diabetes insipidus ••• ••••• Used in combination to manage Edema Combination Product in combination with: Spironolactone (DB00421) •••••••••••• •••••••••• •••••••• •• ••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine.2,3,4,10,11 Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg.10,11 Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.10,11
- Mechanism of action
Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4.6,3 From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).6
Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.4
Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3).2,3,4 Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.4
Target Actions Organism ASolute carrier family 12 member 3 inhibitorHumans AAngiotensin-converting enzyme modulatorHumans ACalcium-activated potassium channel subunit alpha-1 inhibitorHumans - Absorption
An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a Tmax of 1-5 hours, and a Cmax of 70-490ng/mL following doses of 12.5-100mg.10,11 When taken with a meal, bioavailability is 10% lower, Cmax is 20% lower, and Tmax increases from 1.6 to 2.9 hours.11
- Volume of distribution
The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.8
- Protein binding
Hydrochlorothiazide is 40-68% protein bound in plasma.10,11 Hydrochlorothiazide has been shown to bind to human serum albumin.5
- Metabolism
- Route of elimination
Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide.10,11
- Half-life
The plasma half life of hydrochlorothiazide is 5.6-14.8h.10
- Clearance
The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min.7 Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.7
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The oral LD50 of hydrochlorothiazide is >10g/kg in mice and rats.10,11
Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia.10,11,2 Treat patients with symptomatic and supportive treatment including fluids and electrolytes.10,11,2 Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.2,10,11
- Pathways
Pathway Category Hydrochlorothiazide Action Pathway Drug action - 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Hydrochlorothiazide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abaloparatide The risk or severity of adverse effects can be increased when Hydrochlorothiazide is combined with Abaloparatide. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydrochlorothiazide. Acamprosate The excretion of Acamprosate can be decreased when combined with Hydrochlorothiazide. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Hydrochlorothiazide. - Food Interactions
- Avoid alcohol. Alcohol may potentiate orthostatic hypotension.
- Avoid multivalent ions. Take this medication 2 hours before or after the administration of antacids, calcium supplements, or iron supplements to avoid decreased absorption of hydrochlorothiazide.
- Avoid natural licorice. Licorice potentiates the hypokalemic effect of hydrochlorothiazide.
- Increase consumption of potassium-rich foods. This medication may cause potassium depletion. Foods containing potassium include bananas and orange juice.
- Limit salt intake. Avoid excessive salt, unless recommended by a physician.
- Take with or without food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Images
- International/Other Brands
- Dichlotride (M & H) / Esidrex (Novartis) / HydroDIURIL (Merck)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Diuchlor H Tab 50mg Tablet 50 mg Oral Medic Laboratory LtÉe 1964-12-31 1996-09-09 Canada Esidrix Tablet 50 mg/1 Oral Novartis 1959-02-12 2008-08-04 US Esidrix Tablet 25 mg/1 Oral Novartis 1959-02-12 2008-08-04 US Hydrochlorothiazide Tablet 50 mg Oral Sobio Pharmaceutical Canada Inc. Not applicable Not applicable Canada Hydrochlorothiazide Tablet 50 mg Oral Sanis Health Inc 2011-02-08 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-hydrochlorothiazide Tablet 25 mg Oral Apotex Corporation 1975-12-31 Not applicable Canada Apo-hydrochlorothiazide Tablet 100 mg Oral Apotex Corporation 1988-12-31 Not applicable Canada Apo-hydrochlorothiazide Tablet 12.5 mg Oral Apotex Corporation 2009-07-02 Not applicable Canada Apo-hydrochlorothiazide Tablet 50 mg Oral Apotex Corporation 1974-12-31 Not applicable Canada Ava-hydrochlorothiazide Tablet 12.5 mg Oral Avanstra Inc 2011-10-11 2014-08-21 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Aa-amilzide Hydrochlorothiazide (50 mg) + Amiloride hydrochloride (5 mg) Tablet Oral Aa Pharma Inc 1989-12-31 Not applicable Canada AA-Amilzide Tablet 50mg/5mg Hydrochlorothiazide (50 mg) + Amiloride hydrochloride (5 mg) Tablet Oral PHARMAFORTE SINGAPORE PTE LTD 2024-01-17 Not applicable Malaysia Accel-candesartan/hctz Hydrochlorothiazide (12.5 mg) + Candesartan cilexetil (32 mg) Tablet Oral Accel Pharma Inc 2017-12-27 2020-03-05 Canada Accel-candesartan/hctz Hydrochlorothiazide (25 mg) + Candesartan cilexetil (32 mg) Tablet Oral Accel Pharma Inc 2017-12-27 2020-03-05 Canada Accel-candesartan/hctz Hydrochlorothiazide (12.5 mg) + Candesartan cilexetil (16 mg) Tablet Oral Accel Pharma Inc 2017-12-27 2020-03-05 Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Capozide Hydrochlorothiazide (15 mg/1) + Captopril (25 mg/1) Tablet Oral Physicians Total Care, Inc. 1996-05-14 2011-05-31 US Capozide Hydrochlorothiazide (25 mg/1) + Captopril (50 mg/1) Tablet Oral Physicians Total Care, Inc. 1997-01-03 2002-06-30 US
Categories
- ATC Codes
- C09BX03 — Ramipril, amlodipine and hydrochlorothiazide
- C09BX — ACE inhibitors, other combinations
- C09B — ACE INHIBITORS, COMBINATIONS
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- C03AX — Thiazides, combinations with other drugs
- C03A — LOW-CEILING DIURETICS, THIAZIDES
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- C03AB — Thiazides and potassium in combination
- C03A — LOW-CEILING DIURETICS, THIAZIDES
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- C09DX — Angiotensin II receptor blockers (ARBs), other combinations
- C09D — ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- C03EA — Low-ceiling diuretics and potassium-sparing agents
- C03E — DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- C09DX — Angiotensin II receptor blockers (ARBs), other combinations
- C09D — ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- C09XA — Renin-inhibitors
- C09X — OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- G01AE — Sulfonamides
- G01A — ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
- G01 — GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- C09DX — Angiotensin II receptor blockers (ARBs), other combinations
- C09D — ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- C03AA — Thiazides, plain
- C03A — LOW-CEILING DIURETICS, THIAZIDES
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- C09XA — Renin-inhibitors
- C09X — OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- C09DX — Angiotensin II receptor blockers (ARBs), other combinations
- C09D — ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
- C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- Amides
- Antihypertensive Agents
- Antihypertensive Agents Indicated for Hypertension
- Benzothiadiazines
- Cardiovascular Agents
- Diuretics
- Drugs causing inadvertant photosensitivity
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Heterocyclic Compounds, Fused-Ring
- Hyperglycemia-Associated Agents
- Hypotensive Agents
- Increased Diuresis
- Low-Ceiling Diuretics and Potassium-Sparing Agents
- Membrane Transport Modulators
- Natriuretic Agents
- Nephrotoxic agents
- Non Potassium Sparing Diuretics
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Substrates
- Photosensitizing Agents
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Sodium Chloride Symporter Inhibitors
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Thiazides
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thiadiazines
- Sub Class
- Benzothiadiazines
- Direct Parent
- 1,2,4-benzothiadiazine-1,1-dioxides
- Alternative Parents
- Secondary alkylarylamines / Organosulfonamides / Benzenoids / Aryl chlorides / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives
- Substituents
- 1,2,4-benzothiadiazine-1,1-dioxide / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Hydrocarbon derivative / Organic nitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonamide, organochlorine compound, benzothiadiazine (CHEBI:5778)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0J48LPH2TH
- CAS number
- 58-93-5
- InChI Key
- JZUFKLXOESDKRF-UHFFFAOYSA-N
- InChI
- InChI=1S/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)
- IUPAC Name
- 6-chloro-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
- SMILES
- NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1
References
- Synthesis Reference
Frederic J. Nugent, John K. C. Yen, "Process for preparing the combination products of triamterene and hydrochlorothiazide." U.S. Patent US4804540, issued July, 1987.
US4804540- General References
- Pickkers P, Hughes AD, Russel FG, Thien T, Smits P: Thiazide-induced vasodilation in humans is mediated by potassium channel activation. Hypertension. 1998 Dec;32(6):1071-6. doi: 10.1161/01.hyp.32.6.1071. [Article]
- Herman LL, Bashir K: Hydrochlorothiazide . [Article]
- Akbari P, Khorasani-Zadeh A: Thiazide Diuretics . [Article]
- Gamba G: The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009 Oct;297(4):F838-48. doi: 10.1152/ajprenal.00159.2009. Epub 2009 May 27. [Article]
- Balaei F, Ghobadi S: Hydrochlorothiazide binding to human serum albumin induces some compactness in the molecular structure of the protein: A multi-spectroscopic and computational study. J Pharm Biomed Anal. 2019 Jan 5;162:1-8. doi: 10.1016/j.jpba.2018.09.009. Epub 2018 Sep 5. [Article]
- Hasegawa M, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y: Multidrug resistance-associated protein 4 is involved in the urinary excretion of hydrochlorothiazide and furosemide. J Am Soc Nephrol. 2007 Jan;18(1):37-45. doi: 10.1681/ASN.2005090966. Epub 2006 Nov 29. [Article]
- Niemeyer C, Hasenfuss G, Wais U, Knauf H, Schafer-Korting M, Mutschler E: Pharmacokinetics of hydrochlorothiazide in relation to renal function. Eur J Clin Pharmacol. 1983;24(5):661-5. doi: 10.1007/bf00542218. [Article]
- Chen TM, Chiou WL: Large differences in the biological half-life and volume of distribution of hydrochlorothiazide in normal subjects from eleven studies. Correlation with their last blood sampling times. Int J Clin Pharmacol Ther Toxicol. 1992 Jan;30(1):34-7. [Article]
- FDA Approved Drug Products: Esidrix Hydrochlorothiazide Oral Tablets (Discontinued) [Link]
- FDA Approved Drug Products: Hydrochlorothiazide Oral Tablets [Link]
- FDA Approved Drug Products: Hydrochlorothiazide Oral Capsules [Link]
- FDA Approved Drug Products: Losartan and Hydrochlorothiazide Oral Tablets [Link]
- FDA Approved Drug Products: Irbesartan and Hydrochlorothiazide Oral Tablets [Link]
- FDA Approved Drug Products: Lisinopril and Hydrochlorothiazide Oral Tablet [Link]
- FDA Approved Drug Products: Quinapril and Hydrochlorothiazide Oral Tablets [Link]
- FDA Approved Drug Products: HYZAAR (losartan potassium and hydrochlorothiazide) tablets for oral use (March 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0001928
- KEGG Drug
- D00340
- KEGG Compound
- C07041
- PubChem Compound
- 3639
- PubChem Substance
- 46504440
- ChemSpider
- 3513
- BindingDB
- 13076
- 5487
- ChEBI
- 5778
- ChEMBL
- CHEMBL435
- ZINC
- ZINC000000896569
- Therapeutic Targets Database
- DAP000750
- PharmGKB
- PA449899
- PDBe Ligand
- HCZ
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Hydrochlorothiazide
- PDB Entries
- 8pc4 / 9bwt
- MSDS
- Download (72.7 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Hypertension 1 somestatus stop reason just information to hide Not Available Completed Not Available Aging / Hypertension 1 somestatus stop reason just information to hide Not Available Completed Not Available Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Hypertension / Myocardial Infarction 1 somestatus stop reason just information to hide Not Available Completed Not Available Cardiovascular Disease (CVD) / Hypertension 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / COVID / Hypertension 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Apotex inc
- Aurobindo pharma ltd
- Cadista pharmaceuticals inc
- Ipca laboratories ltd
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Mylan pharmaceuticals inc
- Unichem laboratories ltd
- Vintage pharmaceuticals inc
- West ward pharmaceutical corp
- Watson laboratories inc
- Morton grove pharmaceuticals inc
- Roxane laboratories inc
- Novartis pharmaceuticals corp
- Abc holding corp
- Actavis elizabeth llc
- Alra laboratories inc
- Ascot hosp pharmaceuticals inc div travenol laboratories inc
- Barr laboratories inc
- Caraco pharmaceutical laboratories ltd
- Dava pharmaceuticals inc
- Elkins sinn div ah robins co inc
- Excellium pharmaceutical inc
- Heather drug co inc
- Heritage pharmaceuticals inc
- Impax laboratories inc
- Inwood laboratories inc sub forest laboratories inc
- Lannett holdings inc
- Mm mast and co
- Mutual pharmaceutical co inc
- Private formulations inc
- Sandoz inc
- Solvay pharmaceuticals
- Superpharm corp
- Teva pharmaceuticals usa inc
- Tg united labs llc
- Usl pharma inc
- Vangard laboratories inc div midway medical co
- Warner chilcott div warner lambert co
- Whiteworth towne paulsen inc
- Halsey drug co inc
- Merck and co inc
- Abbott laboratories pharmaceutical products div
- Packagers
- Abbott Laboratories Ltd.
- Actavis Group
- Advanced Pharmaceutical Services Inc.
- Aidarex Pharmacuticals LLC
- Amerisource Health Services Corp.
- Apotex Inc.
- Apotheca Inc.
- A-S Medication Solutions LLC
- AstraZeneca Inc.
- Atlantic Biologicals Corporation
- Aurobindo Pharma Ltd.
- Barr Pharmaceuticals
- Boehringer Ingelheim Ltd.
- Bristol-Myers Squibb Co.
- Bryant Ranch Prepack
- BTA Pharmaceuticals
- C.O. Truxton Inc.
- Cadista Pharmaceuticals Inc.
- Calvin Scott and Co. Inc.
- Caraco Pharmaceutical Labs
- Cardinal Health
- Carlisle Laboratories Inc.
- Central Texas Community Health Centers
- Ciba Geigy Ltd.
- Comprehensive Consultant Services Inc.
- Corepharma LLC
- Coupler Enterprises Inc.
- Darby Dental Supply Co. Inc.
- DAVA Pharmaceuticals
- Dee Stevens and Son Feeder
- DHHS Program Support Center Supply Service Center
- Direct Dispensing Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Doctor Reddys Laboratories Ltd.
- Duramed
- E.R. Squibb and Sons LLC
- Endo Pharmaceuticals Inc.
- Eon Labs
- Excellium Pharmaceutical Inc.
- Genpharm LP
- Glenmark Generics Ltd.
- Golden State Medical Supply Inc.
- Goldline Laboratories Inc.
- Greenstone LLC
- Group Health Cooperative
- H and H Laboratories
- H.J. Harkins Co. Inc.
- Heartland Repack Services LLC
- Heritage Pharmaceuticals
- International Laboratories Inc.
- Ipca Laboratories Ltd.
- Ivax Pharmaceuticals
- Kaiser Foundation Hospital
- Kraft Pharmaceutical Co. Inc.
- Lake Erie Medical and Surgical Supply
- Lannett Co. Inc.
- Liberty Pharmaceuticals
- Major Pharmaceuticals
- Mckesson Corp.
- Medisca Inc.
- Medvantx Inc.
- Merck & Co.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Novartis AG
- Nucare Pharmaceuticals Inc.
- Ohm Laboratories Inc.
- Palmetto Pharmaceuticals Inc.
- Par Pharmaceuticals
- Patheon Inc.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmedix
- Pharmpak Inc.
- Physicians Total Care Inc.
- Pliva Inc.
- Preferred Pharmaceuticals Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Qualitest
- Quality Research Pharmaceutical Inc.
- Ranbaxy Laboratories
- Rebel Distributors Corp.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Roxane Labs
- Sandoz
- Solvay Pharmaceuticals
- Southwood Pharmaceuticals
- Stat Rx Usa
- Stat Scripts LLC
- Talbert Medical Management Corp.
- Taro Pharmaceuticals USA
- Teva Pharmaceutical Industries Ltd.
- UDL Laboratories
- Unichem Laboratories Ltd.
- United Research Laboratories Inc.
- Va Cmop Dallas
- Vangard Labs Inc.
- Vintage Pharmaceuticals Inc.
- Watson Pharmaceuticals
- West-Ward Pharmaceuticals
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet Oral 5 mg Tablet Oral 12.5 mg Tablet Oral 16 mg Tablet Oral 12.500 mg Tablet, film coated Oral Tablet Oral 25.000 mg Tablet, coated Oral Tablet, film coated Oral Tablet, film coated Oral 25.0 mg Tablet, film coated Oral 12.50 mg Tablet, film coated Oral 12.5 mg Tablet, film coated Oral 25 mg Tablet, film coated Oral 25.00 mg Tablet, film coated Oral 10.00 mg Tablet, film coated Oral 5.00 mg Tablet Oral 20.00 mg Tablet Oral 1250000 mg Capsule Oral Capsule Oral 12.5 mg/1 Capsule, gelatin coated Oral 12.5 mg/1 Tablet Oral 12.5 mg/1 Tablet Oral 25 mg/1 Tablet Oral 25 mg/25mg Tablet Oral 50 mg/1 Tablet Oral 50 mg/50mg Tablet Oral 100 mg Tablet Oral Tablet Oral Tablet, coated Oral 12.5 mg Tablet, extended release Oral Tablet Oral 12.5 mg Tablet Oral 12.50 mg Tablet Oral 12.500 mg Tablet, film coated, extended release Oral Tablet Oral 25.00 mg/tablet Tablet Oral 12.50 mg Tablet Oral 10.000 mg Tablet, film coated Oral 12.5 mg Tablet, film coated Oral 25 mg Capsule, coated Oral Capsule, liquid filled Oral Tablet Oral 25 mg Tablet Oral 50 mg Tablet - Prices
Unit description Cost Unit Niferex-150 Forte 100 80-70 mg capsule Box 109.86USD box Niferex 100 mg/5ml Elixir 236ml Bottle 80.55USD bottle Niferex 100 40-20 mg capsule Box 77.99USD box Capozide 50-25 mg tablet 3.63USD tablet Ziac 10-6.25 mg tablet 3.6USD tablet Ziac 2.5-6.25 mg tablet 3.6USD tablet Ziac 5-6.25 mg tablet 3.6USD tablet Capozide 50-15 tablet 3.49USD tablet Capozide 50-25 tablet 3.49USD tablet Capozide 50-15 mg tablet 2.59USD tablet Lotensin 20 mg tablet 2.25USD tablet Lotensin 10 mg tablet 2.09USD tablet Lotensin 40 mg tablet 2.09USD tablet Lotensin 5 mg tablet 2.09USD tablet Accuretic 20-12.5 mg tablet 2.04USD tablet Capozide 25-15 tablet 2.03USD tablet Capozide 25-25 tablet 2.03USD tablet Accuretic 10-12.5 mg tablet 2.0USD tablet Accuretic 20-25 mg tablet 2.0USD tablet Lotensin HCT 20-12.5 mg tablet 1.97USD tablet Lotensin HCT 10-12.5 mg tablet 1.95USD tablet Lotensin HCT 20-25 mg tablet 1.94USD tablet Lotensin hct 10-12.5 tablet 1.9USD tablet Lotensin hct 20-12.5 tablet 1.9USD tablet Lotensin hct 20-25 tablet 1.9USD tablet Lotensin hct 5-6.25 tablet 1.9USD tablet Niferex-150 150-50-50 mg capsule 1.62USD capsule Capozide 25-15 mg tablet 1.51USD tablet Lotensin HCT 5-6.25 mg tablet 1.31USD tablet Hydrochlorothiazide powder 1.1USD g Hydrochlorothiazide 12.5 mg tablet 0.82USD tablet Moduretic 5-50 mg tablet 0.68USD tablet Hydrochlorothiazide 12.5 mg capsule 0.5USD capsule Hydrochlorothiazide 50 mg tablet 0.16USD tablet Apo-Hydro 100 mg Tablet 0.13USD tablet Hydrochlorothiazide 25 mg tablet 0.11USD tablet Apo-Hydro 50 mg Tablet 0.06USD tablet Novo-Hydrazide 50 mg Tablet 0.06USD tablet Apo-Hydro 25 mg Tablet 0.04USD tablet Novo-Hydrazide 25 mg Tablet 0.04USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6294197 Yes 2001-09-25 2017-12-18 US US6358986 No 2002-03-19 2020-01-10 US US5559111 Yes 1996-09-24 2019-01-21 US US5616599 Yes 1997-04-01 2016-10-25 US US8618172 No 2013-12-31 2028-07-13 US US6878703 Yes 2005-04-12 2022-05-19 US US8101599 No 2012-01-24 2023-05-16 US US8475839 Yes 2013-07-02 2023-11-16 US US8618174 No 2013-12-31 2021-11-15 US US8183295 No 2012-05-22 2023-05-16 US US5994348 Yes 1999-11-30 2015-12-07 US US9023893 No 2015-05-05 2022-03-03 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 266-268 U.S. Patent 3,163,645. water solubility 722 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP -0.07 HANSCH,C ET AL. (1995) logS -2.62 ADME Research, USCD Caco2 permeability -6.06 ADME Research, USCD pKa 7.9 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 2.24 mg/mL ALOGPS logP -0.16 ALOGPS logP -0.58 Chemaxon logS -2.1 ALOGPS pKa (Strongest Acidic) 9.09 Chemaxon pKa (Strongest Basic) -2.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 118.36 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 63.11 m3·mol-1 Chemaxon Polarizability 25.35 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9202 Blood Brain Barrier - 0.9659 Caco-2 permeable - 0.8956 P-glycoprotein substrate Non-substrate 0.6533 P-glycoprotein inhibitor I Non-inhibitor 0.8624 P-glycoprotein inhibitor II Non-inhibitor 0.8688 Renal organic cation transporter Non-inhibitor 0.8416 CYP450 2C9 substrate Non-substrate 0.7664 CYP450 2D6 substrate Non-substrate 0.8333 CYP450 3A4 substrate Non-substrate 0.6217 CYP450 1A2 substrate Non-inhibitor 0.9401 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9252 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.9569 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9036 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.7986 Biodegradation Not ready biodegradable 0.9964 Rat acute toxicity 2.0666 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9576 hERG inhibition (predictor II) Non-inhibitor 0.9135
Spectra
- Mass Spec (NIST)
- Download (11.5 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 160.3849404 predictedDarkChem Lite v0.1.0 [M-H]- 158.7839714 predictedDarkChem Lite v0.1.0 [M-H]- 154.1231 predictedDeepCCS 1.0 (2019) [M+H]+ 161.0779404 predictedDarkChem Lite v0.1.0 [M+H]+ 168.3554659 predictedDarkChem Lite v0.1.0 [M+H]+ 156.4811 predictedDeepCCS 1.0 (2019) [M+Na]+ 160.3553404 predictedDarkChem Lite v0.1.0 [M+Na]+ 167.8674124 predictedDarkChem Lite v0.1.0 [M+Na]+ 162.57423 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity)
- Specific Function
- ATP binding
- Gene Name
- SLC12A3
- Uniprot ID
- P55017
- Uniprot Name
- Solute carrier family 12 member 3
- Molecular Weight
- 113138.04 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Ran XW, Wang C, Dai F, Jiang JJ, Tong NW, Li XJ, Liang JZ: [A case of Gitelman's syndrome presenting with severe hypocalcaemia and hypokalemic periodic paralysis]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Jul;36(4):583-7. [Article]
- Turner ST, Schwartz GL, Chapman AB, Boerwinkle E: WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension. 2005 Oct;46(4):758-65. Epub 2005 Sep 19. [Article]
- Abuladze N, Yanagawa N, Lee I, Jo OD, Newman D, Hwang J, Uyemura K, Pushkin A, Modlin RL, Kurtz I: Peripheral blood mononuclear cells express mutated NCCT mRNA in Gitelman's syndrome: evidence for abnormal thiazide-sensitive NaCl cotransport. J Am Soc Nephrol. 1998 May;9(5):819-26. [Article]
- Barry EL, Gesek FA, Kaplan MR, Hebert SC, Friedman PA: Expression of the sodium-chloride cotransporter in osteoblast-like cells: effect of thiazide diuretics. Am J Physiol. 1997 Jan;272(1 Pt 1):C109-16. [Article]
- Kurschat C, Heering P, Grabensee B: [Gitelman's syndrome: an important differential diagnosis of hypokalemia]. Dtsch Med Wochenschr. 2003 May 30;128(22):1225-8. [Article]
- Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. [Article]
- Significant Drug–Drug Interactions with Antineoplastics [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity (PubMed:15615692, PubMed:20826823, PubMed:2558109, PubMed:4322742, PubMed:7523412, PubMed:7683654). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (PubMed:10913258, PubMed:1320019, PubMed:1851160, PubMed:19773553, PubMed:7683654, PubMed:7876104). Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin (PubMed:11432860, PubMed:1851160, PubMed:19773553, PubMed:23056909, PubMed:4322742). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (PubMed:15615692, PubMed:2558109, PubMed:4322742, PubMed:6055465, PubMed:6270633, PubMed:7683654). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (PubMed:15615692, PubMed:6208535, PubMed:6270633, PubMed:656131). Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (PubMed:2982830, PubMed:6270633, PubMed:656131). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:26403559, PubMed:7876104, PubMed:8257427, PubMed:8609242). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (PubMed:18077343). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (PubMed:11604391, PubMed:16154999, PubMed:19773553). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (PubMed:10336644, PubMed:2983326, PubMed:7683654, PubMed:9371719). Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region (PubMed:10336644, PubMed:19773553, PubMed:7876104)
- Specific Function
- actin binding
- Gene Name
- ACE
- Uniprot ID
- P12821
- Uniprot Name
- Angiotensin-converting enzyme
- Molecular Weight
- 149713.675 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+) (PubMed:14523450, PubMed:29330545, PubMed:31152168). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)
- Specific Function
- actin binding
- Gene Name
- KCNMA1
- Uniprot ID
- Q12791
- Uniprot Name
- Calcium-activated potassium channel subunit alpha-1
- Molecular Weight
- 137558.115 Da
References
- Pickkers P, Hughes AD, Russel FG, Thien T, Smits P: Thiazide-induced vasodilation in humans is mediated by potassium channel activation. Hypertension. 1998 Dec;32(6):1071-6. doi: 10.1161/01.hyp.32.6.1071. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Balaei F, Ghobadi S: Hydrochlorothiazide binding to human serum albumin induces some compactness in the molecular structure of the protein: A multi-spectroscopic and computational study. J Pharm Biomed Anal. 2019 Jan 5;162:1-8. doi: 10.1016/j.jpba.2018.09.009. Epub 2018 Sep 5. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. [Article]
- Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. [Article]
- Akbari P, Khorasani-Zadeh A: Thiazide Diuretics . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Hasegawa M, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y: Multidrug resistance-associated protein 4 is involved in the urinary excretion of hydrochlorothiazide and furosemide. J Am Soc Nephrol. 2007 Jan;18(1):37-45. doi: 10.1681/ASN.2005090966. Epub 2006 Nov 29. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A11
- Uniprot ID
- Q9NSA0
- Uniprot Name
- Solute carrier family 22 member 11
- Molecular Weight
- 59970.945 Da
References
- Akbari P, Khorasani-Zadeh A: Thiazide Diuretics . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685)
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- ATP-binding cassette sub-family C member 4
- Molecular Weight
- 149525.33 Da
References
- Hasegawa M, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y: Multidrug resistance-associated protein 4 is involved in the urinary excretion of hydrochlorothiazide and furosemide. J Am Soc Nephrol. 2007 Jan;18(1):37-45. doi: 10.1681/ASN.2005090966. Epub 2006 Nov 29. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 14:47