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

Absorption, Distribution and Excretion
Rapidly absorbed after oral administration.
Chlorothiazine is not metabolized but rapidly excreted by the kidneys. 10%–15% of the oral dose is excreted unchanged in the urine. Chlorothiazine crosses the placental barrier but not the blood-brain barrier and is secreted into breast milk.
Chlorothiazine is distributed in the extracellular space and does not accumulate in tissues except in the kidneys.
All thiazide drugs can cross the placental barrier.
In nephrectomized animals, chlorothiazine may be excreted in bile; it undergoes no metabolic alteration.
At a fetal/maternal concentration ratio of 1.1, chlorothiazine takes 60 minutes to appear in the fetus…/Excerpt from a table/
For more complete data on the absorption, distribution, and excretion of chlorothiazine (7 metabolites), please visit the HSDB record page.

---

Metabolism/Metabolites

Chlorothiazine is not metabolized but rapidly excreted by the kidneys.
...Chlorothiazine...is metabolically stable. After intravenous injection into the human body...it is excreted unchanged in the urine.

---

Biological half-life
45-120 minutes
Half-life is 1.5 hours. /Excerpt from table/

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Low-dose chlorothiazide appears to be acceptable during lactation. High-dose use may result in potent diuresis, thereby reducing breast milk production. ◉ Effects on Breastfed Infants No relevant published information was found as of the revision date. ◉ Effects on Lactation and Breast Milk No relevant published information was found as of the revision date. The potent diuretic effects of thiazide and thiazide-like diuretics, fluid restriction, and chest binding have been used to suppress postpartum lactation. The additional effects of diuretics on these effective lactation-suppressing measures have not been studied. There are currently no data on the effects of diuretics on established, sustained lactation. Protein Binding Approximately 40% is bound to plasma proteins.

---

Interactions
...In dogs pre-administered sodium bicarbonate, the urine excreted after administration of thiazide diuretics showed a relatively higher concentration of bicarbonate ions than chloride. /Benzothiazines/
Use of enteric-coated potassium chloride and thiazide diuretics...is associated with a higher incidence of distal ileal jejunal ulcers. /Benzothiazines/
Concomitant use of thiazide diuretics with amiodarone may increase the risk of hypokalemia-related arrhythmias. Thiazide Diuretics
When used concomitantly with thiazide diuretics, the efficacy of coumarin or indanedione derivative anticoagulants may be reduced due to increased blood concentrations of procoagulant factors caused by decreased plasma volume; in addition, the improvement in liver function induced by diuretics may lead to increased synthesis of procoagulant factors; dosage adjustments may be necessary. Thiazide Diuretics
For more (complete) interaction data on chlorothiazide (16 in total), please visit the HSDB record page.

---

Non-human toxicity values
Oral LD50 in rats: 10 g/kg
Intraperitoneal LD50 in rats: 1386 mg/kg
Intravenous LD50 in rats: 200 mg/kg
Oral LD50 in mice: 8 g/kg
For more complete data on non-human toxicity values of chlorothiazide (7 in 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.

Crystalline; white powder. (NTP, 1992)
Chlorothiazine is 4H-1,2,4-benzothiadiazine-1,1-dioxide, in which the hydrogen at position 7 is replaced by chlorine and the hydrogen at position 8 is replaced by a sulfonamide group. It is a diuretic used to treat edema and hypertension. It is both a diuretic and an antihypertensive drug.
A thiazide diuretic with similar effects and uses to hydrochlorothiazide. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 812)
Chlorothiazine is a thiazide diuretic. The physiological effect of chlorothiazide is achieved by increasing diuresis.
Chlorothiazine is a short-acting benzothiadiazine sulfonamide derivative and a typical thiazide diuretic. Chlorothiazine is excreted unchanged via the kidneys.
A thiazide diuretic with similar effects and uses to hydrochlorothiazide. (Excerpt from Martindale Pharmacopoeia, 30th Edition, p. 812)
See also: Chlorothiazine sodium (salt form); Chlorothiazine; Reserpine (one of the components); Chlorothiazine; Methyldopa (one of the components).

---

Drug Indications
Chlorothiazine is indicated for the treatment of congestive heart failure, cirrhosis, and edema associated with corticosteroid and estrogen therapy. Chlorothiazine is also indicated for the treatment of hypertension, either alone or to enhance the efficacy of other antihypertensive drugs in severe hypertension.

---

Mechanism of Action
As a diuretic, chlorothiazide increases the excretion of sodium, chloride, and water by inhibiting the early reabsorption of chloride ions in the distal renal tubules via sodium-chloride cotransporters. Thiazides such as chlorothiazide can also inhibit the transport of sodium ions across renal tubular epithelial cells by binding to thiazide-sensitive sodium-chloride transporters. This leads to increased potassium ion excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of chlorothiazide is not fully understood, but it may be related to its action on carbonic anhydrase in smooth muscle or on high-conductivity calcium-activated potassium channels (KCa channels) also present in smooth muscle. The mechanism by which thiazide diuretics lower blood pressure is not fully understood. /Thiazide diuretics/
…Studies have shown that benzothiadiazides have a direct effect on the transport of sodium and chloride in the renal tubules, and this effect is independent of the inactivation of carbonic anhydrase. Thiazides
Regardless of their ultimate mechanism, diuretic thiazides appear to relax the smooth muscle of peripheral arterioles. Thiazides
Carbonic anhydrase inhibitors do not cause excessive bicarbonate excretion, thus avoiding acidosis.
For more complete data on the mechanisms of action of chlorothiazides (10 in total), please visit the HSDB record page.

---

Therapeutic Uses
Antihypertensive Drugs; Thiazide Diuretics
Thiazide diuretics are the first-line maintenance therapy for outpatients with edema (normal renal function) caused by chronic congestive heart failure. …Their efficacy is poor when edema is accompanied by renal impairment. /Thiazides/
Thiazide diuretics have the greatest value in treating edema caused by chronic heart failure. /Thiazides/
Other less common uses of thiazide diuretics include the treatment of diabetes insipidus and hypercalciuria in patients with recurrent urinary tract stones (calcified stones). /Thiazides/
For more complete data on the therapeutic uses of chlorothiazides (15 in total), please visit the HSDB record page.

---

Drug Warnings
Thiazide drugs should be used with caution in cases of cardiac decompensation or hypertension with significant renal impairment, as they may worsen renal insufficiency. Thiazide diuretics
Veterinary use: As with any potent diuretic, prolonged use may lead to fluid and electrolyte imbalances.
Serve electrolyte levels should be measured regularly in all patients to detect hyponatremia, hypochloremic alkalosis, and hypokalemia.
Thiazide diuretics
Contraindicated in patients with anuria, patients with hypersensitivity to this product or other sulfonamides, and healthy pregnant women with or without edema. Use with caution in patients with kidney disease…and also in patients with impaired liver function.
For more complete data on drug warnings for chlorothiazide (18 in total), please visit the HSDB record page.
Pharmacodynamics

Like other thiazide drugs, chlorothiazide promotes the excretion of water (diuresis). It inhibits the reabsorption of Na⁺/Cl^- in the distal convoluted tubule of the kidney. Thiazide drugs can also cause potassium loss and elevated serum uric acid. Thiazide drugs are commonly used to treat hypertension, but their antihypertensive effect is not necessarily due to their diuretic activity. Thiazide drugs have been shown to prevent hypertension-related diseases and death, but their mechanisms are not fully understood. Thiazide drugs induce vasodilation by activating calcium-activated potassium channels (high conductance) in vascular smooth muscle and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazines affect the reabsorption of electrolytes in the distal renal tubules. At the maximum therapeutic dose, the diuretic effect of all thiazide drugs is roughly the same. Chlorothiazines increase sodium and chloride excretion by roughly equal amounts. Sodium excretion may be accompanied by a small loss of potassium and bicarbonate. After oral administration, 10-15% of the dose is excreted unchanged in the urine. Chlorothiazines can cross the placental barrier but not the blood-brain barrier and are secreted into 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.

---

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.

---

View More

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.

---

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