Chlorthalidone

First approved in 1960

Details

Stereochemistry	RACEMIC
Molecular Formula	C14H11ClN2O4S
Molecular Weight	338.766
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NS(=O)(=O)C1=C(Cl)C=CC(=C1)C2(O)NC(=O)C3=CC=CC=C23

InChI

InChIKey=JIVPVXMEBJLZRO-UHFFFAOYSA-N

InChI=1S/C14H11ClN2O4S/c15-11-6-5-8(7-12(11)22(16,20)21)14(19)10-4-2-1-3-9(10)13(18)17-14/h1-7,19H,(H,17,18)(H2,16,20,21)

HIDE SMILES / InChI

Molecular Formula	C14H11ClN2O4S
Molecular Weight	338.766
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=15dd224a-87ad-48dc-80b1-e8382a452c4c

Chlorthalidone is a diuretic that is used for the treatment of hypertansion and edema. The drug is approved by FDA and either prescribed alone (Chlorthalidone trade name) or in combination with atenolol (Tenoretic trade name), azilsartan kamedoxomil (Edarbyclor) and clonidin (Clorpres). The mechanism of action is associated with activation of sodium and chloride renal excretion.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
renal sodium excretion 4 Target ID: GO:0035812 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=15dd224a-87ad-48dc-80b1-e8382a452c4c	Activator 1447
chloride transport 5 Target ID: GO:0006821 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=15dd224a-87ad-48dc-80b1-e8382a452c4c	Activator 1447

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018760s029lbl.pdf	Palliative		Approved 8583	CHLORTHALIDONE Approved Use Diuretics such as chlorthalidone are indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension. Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Chlorthalidone has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. Launch Date 1981
Edema 23 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=193c85ba-43c2-4be2-82cf-7b394a83390e	Palliative		Approved 8583	CHLORTHALIDONE Approved Use Diuretics such as chlorthalidone are indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension. Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Chlorthalidone has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. Launch Date 1981

C_max

Value	Dose	Co-administered	Analyte	Population
1.529 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4067856	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORTHALIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
93.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4067856	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORTHALIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4067856	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORTHALIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
50 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019574s016lbl.pdf			CHLORTHALIDONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
25% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019574s016lbl.pdf			CHLORTHALIDONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 1 times / day multiple, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13888859/	unhealthy, mean age 47 years Health Status: unhealthy Age Group: mean age 47 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/13888859/	Other AEs: Hypokalemia... Other AEs: Hypokalemia Sources: https://pubmed.ncbi.nlm.nih.gov/13888859/
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/334436/ https://pubmed.ncbi.nlm.nih.gov/354839/	unhealthy, mean age 53.6 years Health Status: unhealthy Age Group: mean age 53.6 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/334436/ https://pubmed.ncbi.nlm.nih.gov/354839/	Other AEs: Dry mouth, Energy decreased... Other AEs: Dry mouth Energy decreased Muscle cramps Nausea Dizziness postural Indigestion Dreaming excessive Constipation Nervousness Headaches Gas Tiredness Trouble falling asleep Urination frequency of Decreased appetite Sources: https://pubmed.ncbi.nlm.nih.gov/334436/ https://pubmed.ncbi.nlm.nih.gov/354839/
75 mg 1 times / day multiple, oral Studied dose Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/354839/	unhealthy, mean age 55.3 years Health Status: unhealthy Age Group: mean age 55.3 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/354839/	Other AEs: Headaches, Dizziness... Other AEs: Headaches (5.3%) Dizziness (15.8%) Cramps (5.3%) Orthostatic hypotension (10.5%) Dry mouth (5.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/354839/
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	unhealthy, mean age 57.2 years Health Status: unhealthy Age Group: mean age 57.2 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	Disc. AE: Blood creatinine increased, Blood urea increased... AEs leading to discontinuation/dose reduction: Blood creatinine increased (0.6%) Blood urea increased (0.6%) Headache (0.6%) Hypokalemia (1.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	unhealthy, mean age 57.2 years Health Status: unhealthy Age Group: mean age 57.2 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	Disc. AE: Blood creatinine increased, Dizziness... AEs leading to discontinuation/dose reduction: Blood creatinine increased (6.4%) Dizziness (3.8%) Hypotension (0.6%) Blood urea increased (0.6%) Headache (0.6%) Fatigue (0.6%) Diarrhea (0.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	unhealthy, mean age 57.2 years Health Status: unhealthy Age Group: mean age 57.2 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	Other AEs: Blood creatinine increased, Dizziness... Other AEs: Blood creatinine increased (18.6%) Dizziness (13.5%) Headache (5.8%) Hypokalemia (3.2%) Blood creatine phosphokinase increased (6.4%) Blood uric acid increased (4.5%) Blood urea increased (5.1%) Diarrhea (3.2%) Fatigue (3.8%) Nasopharyngitis (4.5%) Upper respiratory infection (4.5%) Hyperuricemia (1.9%) Blood potassium decreased (1.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	unhealthy, mean age >59 years Health Status: unhealthy Age Group: mean age >59 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	Other AEs: Dizziness, Headache... Other AEs: Dizziness (3.3%) Headache (7.2%) Plasminogen activator inhibitor increased (1.7%) Hypokalemia (6.1%) Dyslipidemia (2.2%) Asthenia (1.1%) Urinary tract infection (1.7%) Back pain (1.1%) Fatigue (2.8%) Blood uric acid increased (1.1%) Muscle spasms (0.6%) Peripheral edema (2.2%) Upper respiratory tract infection (1.1%) Blood creatine phosphokinase increased (1.7%) Palpitations (2.2%) Hematuria (0.6%) Hypertriglyceridemia (1.1%) Blood potassium decreased (1.7%) Edema (0.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	unhealthy, mean age >59 years Health Status: unhealthy Age Group: mean age >59 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf	Other AEs: Dizziness, Headache... Other AEs: Dizziness (8.7%) Headache (4.3%) Plasminogen activator inhibitor increased (6.5%) Hypokalemia (1.1%) Dyslipidemia (3.8%) Asthenia (3.3%) Urinary tract infection (1.6%) Back pain (3.8%) Fatigue (3.3%) Blood uric acid increased (2.2%) Muscle spasms (2.7%) Peripheral edema (2.2%) Upper respiratory tract infection (2.2%) Blood creatine phosphokinase increased (0.5%) Palpitations (1.6%) Hematuria (1.6%) Hypertriglyceridemia (0.5%) Blood creatinine increased (2.7%) Diarrhea (2.2%) C-reactive protein increased (2.2%) Hypotension (2.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202331Orig1s000MedR.pdf
600 mg 1 times / day single, oral Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: single Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14435310/ https://pubmed.ncbi.nlm.nih.gov/4852369/	healthy Health Status: healthy Sources: https://pubmed.ncbi.nlm.nih.gov/14435310/ https://pubmed.ncbi.nlm.nih.gov/4852369/	Sources: https://pubmed.ncbi.nlm.nih.gov/14435310/ https://pubmed.ncbi.nlm.nih.gov/4852369/
25 mg 1 times / day steady, oral Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02236520	unhealthy Health Status: unhealthy Sources: https://clinicaltrials.gov/ct2/show/NCT02236520	Other AEs: Hypokalemia, Hyponatremia... Other AEs: Hypokalemia (below serious, 1 patient) Hyponatremia (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02236520

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241797/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3654	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3654
ChemicalBook	CB3233539	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3233539
eMolecules	535944	https://www.emolecules.com/cgi-bin/more?vid=535944
MolPort	MolPort-002-736-049	https://www.molport.com/shop/molecule-link/MolPort-002-736-049
Selleck Chemicals	chlorthalidone-chlortalidone	http://www.selleckchem.com/products/chlorthalidone-chlortalidone.html

PubMed

Title	Date	PubMed
A family physician questions the conclusions from ALLHAT.	2004-04	15062891
Metabolic issues in the Antihypertensive and Lipid-Lowering Heart Attack Trial Study.	2004-04	15010012
The 45-year story of the development of an anti-aldosterone more specific than spironolactone.	2004-03-31	15134800
Blockade of the angiotensin II type 1 receptor stabilizes atherosclerotic plaques in humans by inhibiting prostaglandin E2-dependent matrix metalloproteinase activity.	2004-03-30	15037537
[Can hydrochlorothiazide and chlorthalidone be compared in the treatment of hypertension?].	2004-03-18	15039824
Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study.	2004-03	15010644
Foot volume increase on nifedipine is not prevented by pretreatment with diuretics.	2004-02	15076203
Hypothetical economic analysis of screening for left ventricular hypertrophy in high-risk normotensive populations.	2004-02	14747623
Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography.	2004-01-02	14753771
Guidelines for antihypertensive treatment: an update after the ALLHAT study.	2004-01	14684673
Relationship between blood glucose control, pathogenesis and progression of diabetic nephropathy.	2004-01	14684663
Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability.	2004-01	14638621
Effect of antihypertensive agents on quality of life in the elderly.	2004	15084140
Back to thiazide-diuretics for hypertension: reflections after a decade of irrational prescribing.	2003-12-23	14693039
Characteristics and lipid distribution of a large, high-risk, hypertensive population: the lipid-lowering component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).	2003-12-23	14688492
What ALLHAT tells us about treating high-risk patients with hypertension and hyperlipidemia.	2003-12-19	14680343
[Recent intervention studies with antihypertensive drugs and their influence on guidelines].	2003-12-15	14685679
Chemometrics-assisted simultaneous determination of atenolol and chlorthalidone in synthetic binary mixtures and pharmaceutical dosage forms.	2003-12	12955392
Calcium antagonists and atherosclerosis protection in hypertension.	2003-11-19	14624278
Amlodipine or lisinopril was not better than chlorthalidone in lowering CHD risk in hypertension.	2003-11-05	14594435
ALLHAT, or the soft science of the secondary end point.	2003-11-04	14597462
Recommendations for the management of special populations: racial and ethnic populations.	2003-11	14625162
[For every hypertensive patient a diuretic first? "Not advisable in diabetic patients"].	2003-09-11	14584448
The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis.	2003-09-08	12959644
Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).	2003-09	12925554
New evidence on the importance of the renin-angiotensin system in the treatment of higher-risk patients with hypertension.	2003-09	12923384
The Cuban experience in focusing pharmaceuticals policy to health population needs: initial results of the National Pharmacoepidemiology Network (1996-2001).	2003-08-06	12899116
ALLHAT--all hit or all miss? Key questions still remain.	2003-08-01	12888131
Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitors or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).	2003-08	12844462
Amlodipine or lisinopril was not better than chlorthalidone in lowering CHD risk in hypertension.	2003-07-05	12841711
Angiotensin-converting-enzyme inhibitors and diuretics for hypertension.	2003-07-03	12846228
Are thiazide diuretics preferred as first-line therapy for hypertension? An appraisal of The Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT).	2003-07	12823686
ALLHAT: is the final answer in?	2003-06-05	12783629
ALLHAT. Is it all hat?	2003-06-05	12778985
Diuretics: drugs of choice for the initial management of patients with hypertension.	2003-05	15030295
Antihypertensive therapy with verapamil SR plus trandolapril versus atenolol plus chlorthalidone on glycemic control.	2003-05	12745200
ACE inhibitors versus diuretics: ALLHAT versus ANBP2.	2003-05	12740004
[ALLHAT: Old Hat Hits All? On selection of the optimal antihypertensive drug].	2003-03-31	12741071
Trandolapril: a newer angiotensin-converting enzyme inhibitor.	2003-03	12852701
A cheaper way to control high blood pressure.	2003-03	12777218
[The ALLHAT study: contributions, limitations and prospectives].	2003-02	12762256
Diuretics are better first-line antihypertensive therapy than calcium channel blockers and ACE inhibitors.	2003-01-24	12776699
[Diabetes and drug treatment of hypertension].	2003	14679888
Lacidipine: a review of its use in the management of hypertension.	2003	14524737
[Results of clinical evidence: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)].	2003	12968606
[Primary prevention of stroke. What helps--what does not help? The guidelines of the German Society of Neurology briefly summarized].	2003	12958797
[The new (old) knowledge in primary prevention of stroke. It depends on lowering of blood pressure].	2003	12958795
Treatment of isolated systolic hypertension: the SHELL study results.	2003	12875478
Renal hypomagnesemia, hypercalciuria and nephrocalcinosis in a middle-aged man.	2003	12745755
[Severe perioperative hypotension after nephrectomy with adrenalectomy].	2002-04	14606383

Patents

Sample Use Guides

In Vivo Use Guide

Hypertension: starting dose is 25 mg once daily. Edema: 100 mg daily, or 100 mg on alternate days.

Route of Administration: Oral

In Vitro Use Guide

The binding of chlorthalidone to human blood components has been studied in vitro. When the concentration of chlorthalidone in blood was less than 15–20 ug/ml, more than 98% of the compound was bound to red cells. In human serum at 37C, over a concentration range of 0.02–7.7 ug/ml, 75.7% of chlorthalidone was bound to proteins. The association constant with carbonic anhydrase was 2.76×10(6) l/mole.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:47:53 GMT 2025` Edited by `admin` on `Mon Mar 31 18:47:53 GMT 2025`
Record UNII	Q0MQD1073Q
Record Status	`Validated (UNII)`
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Name

Type

Language

CHLORTALIDONE

Preferred Name

English

Chlorthalidone

Official Name

English

HYGROTON

Brand Name

English

CLORPRES COMPONENT CHLORTHALIDONE

Common Name

English

CHLORTALIDONE [EP IMPURITY]

Common Name

English

Benzenesulfonamide, 2-chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)-

Systematic Name

English

G-33182

Code

English

CHLORTALIDONE [JAN]

Common Name

English

COMBIPRES COMPONENT CHLORTHALIDONE

Common Name

English

CHLORTALIDONUM [WHO-IP LATIN]

Common Name

English

chlortalidone [INN]

Common Name

English

Chlortalidone [WHO-DD]

Common Name

English

REGROTON COMPONENT CHLORTHALIDONE

Common Name

English

LOPRESSIDONE COMPONENT CHLORTHALIDONE

Common Name

English

CHLORTALIDONE [WHO-IP]

Common Name

English

CHLORTALIDONE [EP MONOGRAPH]

Common Name

English

CHLORTHALIDONE [USAN]

Common Name

English

CHLORTHALIDONE [USP MONOGRAPH]

Common Name

English

CHLORTALIDONE [MART.]

Common Name

English

DEMI-REGROTON COMPONENT CHLORTHALIDONE

Common Name

English

TENORETIC COMPONENT CHLORTHALIDONE

Common Name

English

PHTHALAMUDINE

Common Name

English

CHLORTHALIDONE [VANDF]

Common Name

English

CHLORTHALIDONE [MI]

Common Name

English

CHLORTHALIDONE [USP-RS]

Common Name

English

KERLEDEX COMPONENT CHLORTHALIDONE

Common Name

English

NSC-69200

Code

English

2-Chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)benzenesulfonamide

Systematic Name

English

3-Hydroxy-3-[4-chloro-3-sulfamylphenyl]phthalimidine

Common Name

English

CHLORTHALIDONE [HSDB]

Common Name

English

CHLORTHALIDONE [ORANGE BOOK]

Common Name

English

NATRIURAN

Common Name

English

THALITONE

Brand Name

English

2-Chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzenesulfonamide

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QC03BA04