Chlorothiazide has a 45–120 minute floral half-life and a nearly 10-hour biological half-life [1].

Absorption, Distribution and Excretion
Rapidly absorbed following oral administration.
Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
CHLOROTHIAZIDE IS DISTRIBUTED THROUGHOUT EXTRACELLULAR SPACE & DOES NOT ACCUMULATE IN TISSUES OTHER THAN THE KIDNEY.
ALL OF THE THIAZIDE-LIKE DRUGS CROSS THROUGH THE PLACENTA.
IN NEPHRECTOMIZED ANIMAL, CHLOROTHIAZIDE MAY BE EXCRETED IN THE BILE; IT DOES NOT UNDERGO METABOLIC ALTERATION.
CHLOROTHIAZIDE IN A 1.1 FETAL/MATERNAL CONCN RATIO REQUIRES 60 MIN TO APPEAR IN FETUS... /FROM TABLE/
For more Absorption, Distribution and Excretion (Complete) data for CHLOROTHIAZIDE (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
Chlorothiazide is not metabolized but is eliminated rapidly by the kidney.
...CHLOROTHIAZIDE...METABOLICALLY STABLE & FOLLOWING IV ADMIN TO...HUMANS...EXCRETED UNCHANGED IN URINE.

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Biological Half-Life
45-120 minutes
Half-life is 1.5 hours. /From Table/

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Low-dose chlorothiazide appears to be acceptable during lactation. Intense diuresis with large doses may decrease breastmilk production.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information on chlorothiazide was not found as of the revision date. Intense diuresis with thiazides and thiazide-like diuretics, fluid restriction and breast binding have been used to suppress postpartum lactation. The added contribution of the diuretic to these measures, which are effective in suppressing lactation, has not been studied. There are no data on the effects of diuretics on established, ongoing lactation.

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Protein Binding
Approximately 40% bound to plasma proteins.

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Interactions
...IN DOG PRELOADED WITH SODIUM BICARBONATE, URINE EXCRETED AFTER ADMIN OF A THIAZIDE CONTAINS RELATIVELY MORE BICARBONATE THAN CHLORIDE. /BENZOTHIADIAZIDES/
USE OF ENTERIC-COATED COMBINATIONS OF POTASSIUM CHLORIDE & THIAZIDE... ASSOCIATED WITH A HIGH INCIDENCE OF ULCERATION OF DISTAL JEJUNUM OF ILEUM. /BENZOTHIADIAZIDES/
Concurrent use of thiazide diuretics with amiodarone may lead to an increased risk of arrhythmias associated with hypokalemia. /Thiazide diuretics/
Effects /of coumarin- or indandione-derivative anticoagulants/ may be decreased when used concurrently with thiazide diuretics as a result of reduction of plasma volume leading to concentration of procoagulant factors in the blood; in addition, diuretic-induced improvement of hepatic function resulting in increased procoagulant factor synthesis; dosage adjustments may be necessary. /Thiazide diuretics/
For more Interactions (Complete) data for CHLOROTHIAZIDE (16 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50Rat oral 10 g/kg
LD50 Rat ip 1386 mg/kg
LD50 Rat iv 200 mg/kg
LD50 Mouse oral 8 g/kg
For more Non-Human Toxicity Values (Complete) data for CHLOROTHIAZIDE (7 total), please visit the HSDB record page.

[1]. Preparation and in-vitro release of chlorothiazide novel pH-sensitive chitosan-N, N′-dimethylacrylamide semi-interpenetrating network microspheres. Carbohydrate Polymers, 2008, 71(2): 208-217.

Crystals; white powder. (NTP, 1992)
Chlorothiazide is 4H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position is substituted by chlorine and that at position 7 is substituted by a sulfonamide group. A diuretic, it is used for treatment of oedema and hypertension. It has a role as a diuretic and an antihypertensive agent.
A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
Chlorothiazide is a Thiazide Diuretic. The physiologic effect of chlorothiazide is by means of Increased Diuresis.
Chlorothiazide is a short-acting, benzothiadiazinesulfonamide derivative and prototypical thiazide diuretic. Chlorothiazide is excreted unchanged by the kidneys.
A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
See also: Chlorothiazide Sodium (has salt form); Chlorothiazide; reserpine (component of); Chlorothiazide; methyldopa (component of).

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Drug Indication
Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.

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Mechanism of Action
As a diuretic, chlorothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like chlorothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of chlorothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
THE MECHANISM BY WHICH THIAZIDE DIURETICS LOWER BLOOD PRESSURE HAS NOT BEEN FIRMLY ESTABLISHED. /THIAZIDE DIURETICS/
...INDICATED THAT BENZOTHIADIAZIDES HAVE A DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE INDEPENDENT OF CARBONIC ANHYDRASE INACTIVATION. /THIADIAZIDES/
IRRESPECTIVE OR ULTIMATE MECHANISM, IT APPEARS THAT DIURETIC THIAZIDES RELAX PERIPHERAL ARTERIOLAR SMOOTH MUSCLE. /THIAZIDES/
CARBONIC ANHYDRASE INHIBITOR WITHOUT EXCESSIVE BICARBONATE EXCRETION WITH RESULTANT ACIDOSIS.
For more Mechanism of Action (Complete) data for CHLOROTHIAZIDE (10 total), please visit the HSDB record page.

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Therapeutic Uses
Antihypertensive Agents; Diuretics, Thiazide
THE THIAZIDES ARE DIURETICS OF CHOICE FOR MAINTENANCE THERAPY IN AMBULATORY PATIENTS WITH EDEMA CAUSED BY CHRONIC CONGESTIVE HEART FAILURE BUT WITH NORMAL RENAL FUNCTION. ...LESS EFFECTIVE WHEN EDEMA IS ASSOCIATED WITH RENAL IMPAIRMENT. /THIAZIDES/
THIAZIDES HAVE THEIR GREATEST USEFULNESS AS DIURETICS IN MGMNT OF EDEMA OF CHRONIC CARDIAC DECOMPENSATION. /THIAZIDES/
LESS COMMON USAGES OF THIAZIDES INCL TREATMENT OF DIABETES INSIPIDUS & MANAGEMENT OF HYPERCALCIURIA IN PT WITH RECURRENT URINARY CALCULI COMPOSED OF CALCIUM. /THIAZIDES/
For more Therapeutic Uses (Complete) data for CHLOROTHIAZIDE (15 total), please visit the HSDB record page.

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Drug Warnings
WHEN CARDIAC DECOMPENSATION OR HYPERTENSION IS ACCOMPANIED BY SIGNIFICANT IMPAIRMENT OF RENAL FUNCTION, THIAZIDES SHOULD BE ADMIN WITH CAUTION BECAUSE OF THEIR CAPACITY TO AGGRAVATE RENAL INSUFFICIENCY. /THIAZIDES/
VET USE: AS WITH ANY POTENT DIURETIC, FLUID & ELECTROLYTE IMBALANCE MAY OCCUR ESP AFTER PROLONGED USE.
PERIODIC SERUM ELECTROLYTE DETERMINATIONS SHOULD BE DONE ON ALL PATIENTS IN ORDER TO DETECT...HYPONATREMIA, HYPOCHLOREMIC ALKALOSIS, & HYPOKALEMIA. /THIAZIDES/
...CONTRAINDICATED IN ANURIA, PATIENTS HYPERSENSITIVE TO THESE & OTHER SULFONAMIDE DRUGS, & IN OTHERWISE HEALTHY PREGNANT WOMEN WITH OR WITHOUT EDEMA. ...SHOULD BE USED WITH CAUTION IN PATIENTS WITH RENAL DISEASE...ALSO... PATIENTS WITH IMPAIRED LIVER FUNCTION.
For more Drug Warnings (Complete) data for CHLOROTHIAZIDE (18 total), please visit the HSDB record page.

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Pharmacodynamics
Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na⁺/Cl^- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.

294.948

58-94-6

Chlorothiazide sodium;7085-44-1;Chlorothiazide-13C,15N2;1189440-79-6

2720

White to off-white solid powder

2.0±0.1 g/cm3

608.8±65.0 °C at 760 mmHg

342-343°C

322.0±34.3 °C

0.0±1.7 mmHg at 25°C

1.801

-0.18

2

6

1

17

532

0

O=S(C1=C(Cl)C=C(C2=C1)N=CNS2(=O)=O)(N)=O

JBMKAUGHUNFTOL-UHFFFAOYSA-N

InChI=1S/C7H6ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-3H,(H,10,11)(H2,9,12,13)

6-chloro-1,1-dioxo-4H-1λ6,2,4-benzothiadiazine-7-sulfonamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~338.16 mM)

Solubility in Formulation 1: ≥ 3.5 mg/mL (11.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 3.5 mg/mL (11.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3.5 mg/mL (11.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)