- Accession Number
- DB00524 (APRD01109)
- Small Molecule
A quinazoline-sulfonamide that is considered a thiazide-like diuretic which is long-acting so useful in chronic renal failure. It also tends to lower blood pressure and increase potassium loss.
- External IDs
- SR 720-22 / SR-720-22
- Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Metolazone Tablet 5 mg/1 Oral H.j. Harkins Co., Inc. 2017-12-08 Not applicable Mykrox Tablets Tablet 500 ug/1 Oral UNSPECIFIED 2006-01-12 Not applicable Zaroxolyn Tablet 2.5 mg/1 Oral Carilion Materials Management 1973-11-27 Not applicable Zaroxolyn Tablet 2.5 mg Oral Sanofi Aventis 1974-12-31 Not applicable Zaroxolyn Tablet 5 mg/1 Oral Unither Pharmaceuticals 1973-11-27 2015-11-30 Zaroxolyn Tablet 5 mg/1 Oral Physicians Total Care, Inc. 1973-11-27 2012-06-30 Zaroxolyn Tablet 2.5 mg/1 Oral Physicians Total Care, Inc. 1973-11-27 2010-06-30 Zaroxolyn Tablet 5 mg Oral Aventis Pharma Ltd. 1974-12-31 2003-07-22 Zaroxolyn Tablet 2.5 mg/1 Oral Unither Pharmaceuticals 1973-11-27 2015-04-30 Zaroxolyn Tab 10mg Tablet 10 mg Oral Rhone Poulenc Rorer 1974-12-31 1998-08-12
- Generic Prescription Products
- International/Other Brands
- Diulo / Diurem (Cipla) / Metadure (Micro Labs) / Metenix (IFET) / Metolaz (Navana) / Metoral (Dr. Reddy's) / Metoz (Centaur) / Metozone (Ying Yuan) / Mykrox (Celltech) / Pavedal (Pharma Investi) / Xuret / Zaroxolyn / Zytanix (Zydus)
- Antihypertensive Agents
- Cardiovascular Agents
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Hyperglycemia-Associated Agents
- Hypotensive Agents
- Increased Diuresis
- Low-Ceiling Diuretics and Potassium-Sparing Agents
- Low-Ceiling Diuretics, Excl. Thiazides
- Membrane Transport Modulators
- Natriuretic Agents
- Non Potassium Sparing Diuretics
- Sodium Chloride Symporter Inhibitors
- Sulfur Compounds
- Thiazide-like Diuretic
- CAS number
- Average: 365.835
- Chemical Formula
- InChI Key
- IUPAC Name
For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.
- Associated Conditions
Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.
- Mechanism of action
The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.
Target Actions Organism ASolute carrier family 12 member 3inhibitor Humans
Peak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent.
- Volume of distribution
- Not Available
- Protein binding
50-70% bound to erythrocytes, up to 33% bound to plasma proteins, 2-5% of the drug in circulation is unbound
Not substantially metabolized. 70-95% is excreted unchanged in urine via glomerular filtration and active tubular secretion. Undergoes enterohepatic recycling.
- Route of elimination
Most of the drug is excreted in the unconverted form in the urine.
- Half life
Approximately 14 hours.
- Not Available
Symptoms of overdose include difficulty breathing, dizziness, dizziness on standing up, drowsiness, fainting, irritation of the stomach and intestines, and lethargy leading to coma.
- Affected organisms
- Humans and other mammals
Pathway Category Metolazone Action Pathway Drug action
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid The risk or severity of hypotension can be increased when Metolazone is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 1alpha-Hydroxyvitamin D5 The risk or severity of hypercalcemia can be increased when Metolazone is combined with 1alpha-Hydroxyvitamin D5. 2,4-thiazolidinedione The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Metolazone. Abacavir Metolazone may decrease the excretion rate of Abacavir which could result in a higher serum level. Abediterol Abediterol may increase the hypokalemic activities of Metolazone. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Metolazone. Acebutolol The risk or severity of adverse effects can be increased when Metolazone is combined with Acebutolol. Aceclofenac The therapeutic efficacy of Metolazone can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Metolazone can be decreased when used in combination with Acemetacin. Acetaminophen Acetaminophen may decrease the excretion rate of Metolazone which could result in a higher serum level.
- Food Interactions
- Take with food to reduce gastric irritation.
- General References
- Rosenberg J, Gustafsson F, Galatius S, Hildebrandt PR: Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature. Cardiovasc Drugs Ther. 2005 Aug;19(4):301-6. [PubMed:16189620]
- External Links
- Human Metabolome Database
- KEGG Drug
- PubChem Compound
- PubChem Substance
- Therapeutic Targets Database
- RxList Drug Page
- Drugs.com Drug Page
- PDRhealth Drug Page
- ATC Codes
- C03EA12 — Metolazone and potassium-sparing agents
- C03EA — Low-ceiling diuretics and potassium-sparing agents
- C03E — DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- C03BA — Sulfonamides, plain
- C03B — LOW-CEILING DIURETICS, EXCL. THIAZIDES
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- AHFS Codes
- 40:28.24 — Thiazide-like Diuretics
- FDA label
- Download (834 KB)
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Not Available Healthy Volunteers 3 1 Recruiting Treatment Congestive Heart Failure (CHF) / Prophylaxis of cardiomyopathy 1 4 Completed Treatment Heart Failure, Unspecified 1 4 Completed Treatment Rapid Ventricular Response Atrial Fibrillation 1 4 Enrolling by Invitation Treatment Acute Heart Failure (AHF) / Cardiovascular Disease (CVD) / Heart Failure With Reduced Ejection Fraction (HFrEF) / Heart Failure, Unspecified 1 4 Not Yet Recruiting Treatment Acute Heart Failure (AHF) / Fluid Overload 1 4 Terminated Treatment Acute Decompensated Heart Failure (ADHF) 1 Not Available Unknown Status Treatment Hypernatremia / Respiratory Failure / Volume Overload 1 Not Available Withdrawn Treatment Congestive Heart Failure (CHF) 2
- Gd searle llc
- Mylan pharmaceuticals inc
- Roxane laboratories inc
- Sandoz inc
- Teva pharmaceuticals usa inc
- Watson laboratories inc
- Ucb inc
- Amerisource Health Services Corp.
- Cardinal Health
- Caremark LLC
- Diversified Healthcare Services Inc.
- Eon Labs
- Mckesson Corp.
- Murfreesboro Pharmaceutical Nursing Supply
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Prepackage Specialists
- Resource Optimization and Innovation LLC
- Sandhills Packaging Inc.
- Southwood Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- UCB Pharma
- UDL Laboratories
- Upstate Pharma LLC
- Vangard Labs Inc.
- Dosage forms
Form Route Strength Tablet Oral 10 mg/1 Tablet Oral 2.5 mg/1 Tablet Oral 5 mg/1 Tablet Oral 500 ug/1 Tablet Oral 2.5 mg Tablet Oral 5 mg Tablet Oral 10 mg
Unit description Cost Unit Zaroxolyn 10 mg tablet 2.89USD tablet Zaroxolyn 5 mg tablet 2.75USD tablet Metolazone 10 mg tablet 1.8USD tablet Zaroxolyn 2.5 mg tablet 1.74USD tablet Metolazone 5 mg tablet 1.51USD tablet Metolazone 2.5 mg tablet 1.37USD tabletDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
- Not Available
- Experimental Properties
Property Value Source melting point (°C) 256 °C PhysProp water solubility 60.3 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 2.5 Not Available logS -3.78 ADME Research, USCD
- Predicted Properties
Property Value Source Water Solubility 0.0407 mg/mL ALOGPS logP 3.21 ALOGPS logP 2.94 ChemAxon logS -4 ALOGPS pKa (Strongest Acidic) 9.54 ChemAxon pKa (Strongest Basic) -1.6 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 92.5 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 94.59 m3·mol-1 ChemAxon Polarizability 36.38 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon
- Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9972 Blood Brain Barrier + 0.5944 Caco-2 permeable - 0.8957 P-glycoprotein substrate Non-substrate 0.7578 P-glycoprotein inhibitor I Non-inhibitor 0.8113 P-glycoprotein inhibitor II Non-inhibitor 0.5921 Renal organic cation transporter Non-inhibitor 0.9223 CYP450 2C9 substrate Non-substrate 0.6466 CYP450 2D6 substrate Non-substrate 0.8279 CYP450 3A4 substrate Non-substrate 0.579 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.923 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.831 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5788 Ames test Non AMES toxic 0.8234 Carcinogenicity Non-carcinogens 0.7193 Biodegradation Not ready biodegradable 0.9961 Rat acute toxicity 1.8955 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9922 hERG inhibition (predictor II) Non-inhibitor 0.8735
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-0aor-1494000000-aae5f0a5c86e9d0828e2 MS/MS Spectrum - , positive LC-MS/MS splash10-0bvi-2960000000-1eed022b28a6bb140f60
- This compound belongs to the class of organic compounds known as quinazolines. These are compounds containing a quinazoline moiety, which is made up of two fused six-member aromatic rings, a benzene ring and a pyrimidine ring.
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Sub Class
- Direct Parent
- Alternative Parents
- Toluenes / Secondary alkylarylamines / Organosulfonamides / Aryl chlorides / Vinylogous amides / Tertiary carboxylic acid amides / Aminosulfonyl compounds / Lactams / Amino acids and derivatives / Azacyclic compoundsOrganopnictogen compounds / Organooxygen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives show 5 more
- Quinazoline / Secondary aliphatic/aromatic amine / Toluene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Organosulfonic acid amide / Organic sulfonic acid or derivatives / Vinylogous amideAminosulfonyl compound / Tertiary carboxylic acid amide / Sulfonyl / Organosulfonic acid or derivatives / Amino acid or derivatives / Carboxamide group / Lactam / Carboxylic acid derivative / Secondary amine / Azacycle / Organic oxide / Organosulfur compound / Organooxygen compound / Organonitrogen compound / Organochloride / Organohalogen compound / Amine / Organopnictogen compound / Organic oxygen compound / Organic nitrogen compound / Hydrocarbon derivative / Aromatic heteropolycyclic compound show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonamide, organochlorine compound, quinazolines (CHEBI:64354)
- Pharmacological action
- General Function
- Transporter activity
- Specific Function
- Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
- Gene Name
- Uniprot ID
- Uniprot Name
- Solute carrier family 12 member 3
- Molecular Weight
- 113138.04 Da
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Drug created on June 13, 2005 07:24 / Updated on January 22, 2019 17:56