Absorption, Distribution and Excretion
Hydrofluorothiazide is incompletely but rapidly absorbed from the gastrointestinal tract. Thiazide drugs are absorbed via the gastrointestinal tract, and their efficacy is primarily attributed to the oral route. Absorption is relatively rapid. Most drugs show significant diuretic effects within 1 hour of oral administration. /Thiazide Diuretics/ Generally, thiazide drugs with a relatively long duration of action have high plasma protein binding rates and are reabsorbed by the renal tubules. The drugs readily cross the placental barrier into the fetus. All thiazide drugs are likely actively secreted in the proximal renal tubules. /Thiazide Diuretics/ Following intravenous infusion of hydrofluorothiazide, there are two distribution phases with half-lives of 0.26 hours and 0.85 hours, respectively. After a single oral dose of 2 μmol/kg, the β-phase half-life is shorter than that after 6 μmol/kg, with mean β-phase half-lives of 8.7 hours and 17.9 hours, respectively.
After oral administration of hydrofluorothiazide every 24 hours for 7 consecutive days, the mean biological half-life was 6.85 hours; the mean half-life of the metabolites was 17.7 hours. 0.652 mg of the dose was excreted unchanged in the urine, and 0.049 mg was excreted as a metabolite. The mean renal plasma clearance was 0.356 L/HR/kg.
For more complete data on the absorption, distribution, and excretion of hydrofluorothiazide (8 metabolites), please visit the HSDB record page.
Metabolism/Metabolites
Substantially unchanged
After oral administration of 100 mg every 24 hours for 7 consecutive days in healthy men, the metabolite 2,4-disulfonyl-5-trifluoromethylaniline was determined.
Biological half-life
Its biological half-life is biphasic, with an estimated α phase of approximately 2 hours and an estimated β phase of approximately 17 hours.
The half-life ranges from 12 to 27 hours. /Excerpt from the table/
/ The estimated distribution half-life of hydrofluorothiazide is approximately 2 hours, and the estimated terminal elimination half-life is approximately 17 hours...

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
There is currently no information on the content of hydrofluorothiazide in breast milk. High-dose potent diuretics may reduce breast milk production. It is recommended to prioritize other low-dose diuretics over hydrofluorothiazide.
◉ 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 continuous lactation.

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Protein binding
74%Interactions
...Use of diuretics (thiazides) that can increase plasma uric acid levels may interfere with uricosuric therapy.../Thiazide diuretics/
Concomitant use of thiazide diuretics and monoamine oxidase inhibitors may increase hypotension. /Thiazide diuretics/
Electrolyte disturbances caused by hydrofluorothiazide may make patients susceptible to.../Digitalis toxicity. Severe potassium deficiency may occur when used in combination with corticosteroids, adrenocorticotropic hormone, and amphotericin B. May antagonize the effects of oral anticoagulants. Hydrofluorothiazide may prolong the neuromuscular blocking effect of non-depolarizing neuromuscular blocking agents (such as tubocurarine chloride or gallium triiodide). Reduced renal clearance of lithium. Serum lithium levels may be elevated in patients receiving lithium carbonate and long-term diuretic therapy. For more complete data on hydrofluorothiazide interactions (22 in total), please visit the HSDB record page.

[1].Selvaag E, et al. Phototoxicity to sulphonamide derived oral antidiabetics and diuretics. Comparative in vitro and in vivo investigations. In Vivo. 1997 Jan-Feb;11(1):103-7.

[2].Br\u00f8rs O, et al. Pharmacokinetics of a single oral dose of hydroflumethiazide in health and in cardiac failure.-. Eur J Clin Pharmacol. 1978 Nov 9;14(1):29-37.

[3].Hermansen K, et al. Effects of a thiazide diuretic (hydroflumethiazide) and a loop diuretic (bumetanide) on the endocrine pancreas: studies in vitro. Metabolism. 1985 Aug;34(8):784-9.

Hydrofluorothiazide is a benzothiadiazine drug, composed of a 3,4-dihydro-1,2,4-benzothiadiazine bicyclic system, with sulfur atoms substituted with dioxygen atoms, and trifluoromethyl and aminosulfonyl groups attached at positions 6 and 7, respectively. It is a diuretic, with effects and uses similar to hydrochlorothiazide. It is both a diuretic and an antihypertensive drug. It belongs to the benzothiadiazine and thiazide classes of drugs.
A thiazide diuretic, with effects and uses similar to hydrochlorothiazide. (Excerpt from Martindale Pharmacopoeia, 30th edition, page 822)
Hydrofluorothiazide is a thiazide diuretic. The physiological effect of hydrofluorothiazide is achieved by increasing diuresis.
Hydrofluorothiazide is a medium-acting benzothiadiazine sulfonamide derivative, belonging to the thiazide diuretic class.
A thiazide diuretic, with effects and uses similar to hydrochlorothiazide. (Excerpt from Martindale Pharmacopoeia, 30th Edition, p. 822)
See also: hydrofluorothiazide; reserpine (components).
Indications

For the treatment of congestive heart failure, cirrhosis, and edema associated with corticosteroid and estrogen therapy. Also used to treat hypertension, either alone or to enhance the efficacy of other antihypertensive drugs in severe hypertension.
Mechanism of Action

Hydrofluorothiazide is a thiazide diuretic that inhibits the reabsorption of water by nephrons by inhibiting the sodium-chloride cotransporter (SLC12A3) in the distal convoluted tubule. This protein is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride cotransporter transports sodium and chloride from the lumen into the epithelial cells of the distal convoluted tubule. The energy required for this process comes from the sodium ion gradient established by sodium-potassium ATPase on the basolateral membrane. After sodium ions enter the cell, they are transported to the basolateral interstitium via sodium-potassium ATPase, leading to an increase in interstitial osmotic pressure and establishing an osmotic gradient for water reabsorption. Hydrofluorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron by blocking sodium-chloride cotransporters. Benzothiadiazides have a direct effect on the transport of sodium and chloride in the renal tubules…and are independent of any effect on carbonic anhydrase. /Thiazide Diuretics/ The chemical interaction mechanism between thiazides and the specific renal receptors responsible for chloride diuresis is unclear; the key enzymatic reactions have not been identified. Thiazides inhibit the reabsorption of sodium and chloride in the distal renal tubules. …As a class of drugs…they play an important role in potassium excretion resulting from increased cation secretion in the distal renal tubules. …Thiazides can reduce glomerular filtration rate, especially when administered intravenously for experimental purposes. Thiazides reduce the excretion of uric acid in the body, thereby increasing the concentration of uric acid in the plasma. The hyperuricemic effect primarily stems from the inhibition of renal tubular secretion of urate. …Unlike most other diuretics…it reduces renal calcium excretion (relative to sodium excretion)…/enhances/magnesium excretion…/thiazides/
For more complete data on the mechanisms of action of hydrofluorothiazides (11 in total), please visit the HSDB record page.

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Therapeutic Uses
Antihypertensive; Thiazide Diuretics
A potent oral diuretic used to treat heart failure, cirrhosis, premenstrual syndrome, and edema induced by steroid administration.Also recommended for the treatment of mild to moderate hypertension, either alone or in combination with other antihypertensive drugs.
Except for the lower doses required for hydrofluorothiazides…there is no convincing evidence that hydrofluorothiazides differ significantly from their parent compound, fluothiazide, or the precursor drug, chlorothiazide, in terms of treatment, metabolism, toxicity, or sensitization in patients with edema or hypertension.
Refractory cases may require doses up to 200 mg daily in divided doses. Dosage should be adjusted to provide the minimum effective dose for the individual patient. For more complete data on the therapeutic uses of hydrofluorothiazides (11 in total), please visit the HSDB record page.

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Drug Warnings
Serve electrolyte measurements should be performed regularly in all patients to detect electrolyte imbalances such as hyponatremia, hypochloremic alkalosis, and hypokalemia. Thiazide Diuretics
Thiazide diuretics are contraindicated in patients with anuria, patients with hypersensitivity to thiazide diuretics or other sulfonamides, and healthy pregnant women with or without mild edema. …Caution should be exercised in patients with kidney disease due to the possibility of azotemia. Thiazide Diuretics
One of the most common adverse reactions to thiazide diuretics is potassium loss, which occurs in most patients. Potassium loss can lead to arrhythmias, which is particularly important in patients taking cardiac glycosides, as hypokalemia can enhance the cardiotoxicity of these drugs (e.g., increased ventricular excitability). Patients with primary or secondary hyperaldosteronism, low potassium intake, taking other potassium-depleting medications, or those experiencing potassium loss due to vomiting or diarrhea may have particularly low serum potassium levels. Intermittent, non-continuous use of thiazide diuretics and/or consumption of potassium-rich foods may reduce or prevent potassium loss; however, for patients with serum potassium levels below approximately 3 mEq/L, prophylactic potassium supplementation, such as potassium chloride solution or potassium-sparing diuretics, may be necessary. Enteric-coated potassium tablets should not be used due to the potential for gastrointestinal ulceration. /Thiazide Diuretics/
Hypercalcemia may also occasionally occur in patients taking thiazide diuretics, especially in those taking vitamin D or with mild hyperparathyroidism. Hypomagnesemia may also occur. /Thiazides/
For more complete data on drug warnings for hydrofluorothiazide (24 in total), please visit the HSDB record page.

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Pharmacodynamics
Hydrofluorothiazide is an oral thiazide drug used to treat hypertension and edema. High blood pressure increases the burden on the heart and arteries. If it persists for a long time, the heart and arteries may fail to function properly. This can damage blood vessels in the brain, heart, and kidneys, leading to stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attack. Like other thiazide drugs, hydrofluorothiazides promote the excretion of water from the body (diuretics). Thiazides inhibit the reabsorption of sodium/chloride ions in the distal convoluted tubule of the kidneys. Thiazides also cause potassium loss and elevated serum uric acid. Thiazides are commonly used to treat hypertension, but their blood pressure-lowering effect is not entirely attributable to their diuretic activity. Although the mechanism is not fully understood, thiazides have been shown to prevent hypertension-related morbidity and mortality. Thiazides induce vasodilation by activating calcium-activated potassium channels (large conductance channels) in vascular smooth muscle and inhibiting various carbonic anhydrases in vascular tissue.

C8H8F3N3O4S2

331.29

330.991

135-09-1

Hydroflumethiazide-13C,d2;1189877-11-9;Hydroflumethiazide-15N2,13C,d2

3647

CRYSTALS
White to cream colored, finely divided, crystalline powder

1.678g/cm3

531.6ºC at 760 mmHg

272-273ºC

275.3ºC

2.2E-11mmHg at 25°C

1.55

3.342

3

10

1

20

578

0

C1=C(C(=CC2=C1NCNS2(=O)=O)S(=O)(=O)N)C(F)(F)F

DMDGGSIALPNSEE-UHFFFAOYSA-N

InChI=1S/C8H8F3N3O4S2/c9-8(10,11)4-1-5-7(2-6(4)19(12,15)16)20(17,18)14-3-13-5/h1-2,13-14H,3H2,(H2,12,15,16)

1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1λ6,2,4-benzothiadiazine-7-sulfonamide

Glomerulin Diuredemina Hydroflumethiazide

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 : ~125 mg/mL (~377.32 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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