NaH2PO4, sometimes known as dihydrogen monosodium phosphate, is a mixture of counterions for sodium and phosphate. When combined with other sodium phosphates, dihydrogen monosodium phosphate functions as a pH buffer. Dihydrogen monosodium phosphate is a useful excipient in medicinal products that are used as chelating agents and buffers. Other chemicals utilized in the pharmaceutical process besides medication components are referred to as pharmaceutical auxiliaries or excipients. Pharmaceutical preparations' inactive substances, which can increase their stability, solubility, and processability, are referred to as pharmaceutical excipients. The process of co-administered drug absorption, distribution, metabolism, and elimination (ADME) can be impacted by pharmaceutical excipients [1][2].

Absorption, Distribution and Excretion
Following oral administration of liquid sodium phosphate, the time to peak phosphate absorption (Tmax) is 1–3 hours. …Phosphate absorption is slow and incomplete… /Disodium hydrogen phosphate and sodium dihydrogen phosphate/ Almost all of the phosphorus infused intravenously that is not absorbed by tissues is excreted in the urine. Plasma phosphorus is thought to be filtered by the glomeruli, and most of the filtered phosphorus (over 80%) is actively reabsorbed by the renal tubules. Many factors affect the amount of phosphorus excreted in urine. An open-label pharmacokinetic study in healthy volunteers aimed to determine the concentration-time profile of serum inorganic phosphorus levels after administration of Visicol. All subjects received a total of 60 g of sodium phosphate and a total fluid volume of 3.6 quarts. Subjects began taking a 30-gram dose (20 tablets, 3 tablets every 15 minutes, taken with 8 ounces of clear liquid) at 6 p.m. the following day, followed by a second 30-gram dose (20 tablets, 3 tablets every 15 minutes, taken with 8 ounces of clear liquid) at 6 a.m. the next morning. A total of 23 healthy subjects (mean age 57 years; 57% male, 43% female; 65% Hispanic, 30% White, 4% African American) participated in this pharmacokinetic study. Following the first 30-gram dose of vecicotinamide tablets, serum phosphorus levels increased from a mean (± standard deviation) baseline of 4.0 (±0.7) mg/dL to 7.7 (±1.6) mg/dL (median 3 hours after the first 30-gram dose of vecicotinamide tablets). Following administration of the second dose of 30g vesicocort tablets, serum phosphorus levels increased to a mean of 8.4 (±1.9) mg/dL (median 4 hours after administration of the second dose of 30g vesicocort tablets). Following administration of the first dose of vesicocort tablets, serum phosphorus levels remained above baseline for a median of 24 hours (range 16 to 48 hours).

Toxicity Summary
Identification and Uses: Sodium dihydrogen phosphate is a white crystalline powder. It is used as a pH buffer in baking powders; in boiler water treatment; and as a dry acidifier and chelating agent in food. Additionally, it is used as a buffer (electroplating solutions); an acidifier (processed meats, egg products, powdered beverages); an adjuvant (industrial cleaning formulations); a metal phosphating agent; a mineral supplement; a softening/conditioning agent (boiler water treatment); and a textile dyeing/printing auxiliary. Medically, it is used as an enema solution. Human Exposure and Toxicity: Intentional or unintentional ingestion of tablets exceeding the recommended dose may result in serious electrolyte disturbances, including hyperphosphatemia, hypocalcemia, hypernatremia, or hypokalemia, as well as dehydration and hypovolemia, with signs and symptoms of these disturbances. Some serious electrolyte disturbances may lead to arrhythmias, seizures, kidney failure, or even death. QT interval prolongation has been observed in patients taking Viscolite tablets (sodium dihydrogen phosphate monohydrate and disodium hydrogen phosphate anhydrous). QT interval prolongation caused by vesicochlor tablets is associated with electrolyte imbalances, such as hypokalemia and hypocalcemia. The estimated lethal dose of sodium phosphate is 50 g. Oral sodium phosphate-induced colonic mucosal abnormalities are uncommon, but their symptoms may resemble those caused by nonsteroidal anti-inflammatory drugs (NSAIDs) or inflammatory bowel disease, and should be differentiated from Crohn's disease. Animal studies: Oral administration of 250 g/kg of sodium phosphate caused diarrhea in rats, guinea pigs, and rabbits. In rats treated with sodium dihydrogen phosphate for 6 consecutive days, persistent calcification of the basement membrane of the proximal tubules in the mid-cortex was observed; after 10 days, casts and basement membrane calcification appeared in the outer medulla and renal papillae. Injection of 10.0 mg/egg of sodium dihydrogen phosphate into the air cells and yolk of chicken embryos can cause deformities such as body shape abnormalities, encephalocele, microcephaly, brachygnathia, cardiac hyperplasia, anapexy, torticollis, microphthalmia, anophthalmia, exophthalmos, limb shortening, phocomelia, oxeye, and cleft palate. In vitro mammalian chromosomal aberration assays in unactivated Chinese hamster lung fibroblasts were negative. Genotoxicity studies of Escherichia coli PQ37 and PQ35 using the SOS chromate test were negative regardless of metabolic activation.

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Interactions
When rats were simultaneously administered 5-50 mmol of calcium chloride solution via gavage or orthotopic ligation of the jejunal loops, sodium dihydrogen phosphate and sodium glycerophosphate inhibited intestinal calcium absorption in rats.
The effects of disodium hydrogen phosphate buffer on the intraocular release and ocular and systemic absorption of timolol based on polymethyl methacrylate monoisopropyl ester/maleic anhydride were investigated in rabbits. The vasoconstrictor phenoxysildenafil (P-methoxazole) was added to some of the buffers to reduce systemic absorption of timolol. Compared to the buffered buffer, the unbuffered buffer produced lower peak concentrations of timolol in the tear film and also lower steady-state concentrations in plasma after 3 hours. Therefore, disodium hydrogen phosphate increased the rate of timolol release from the implant into the tear film several times over. Concomitant use of phenylephrine in the buffered buffer reduced the peak plasma concentration of timolol by approximately 3-fold, while increasing the peak tear concentration by approximately 2-fold. In the iridociliary body, the concentration of timolol after using the buffered buffer was comparable to that after eye drops were instilled. Compared to the unbuffered buffer, disodium hydrogen phosphate at least doubled the iridociliary body to plasma concentration ratio, regardless of whether it was used in combination with phenylephrine. This study investigated the effects of aluminum on phosphate processing in rat kidneys. Male Sprague Dawley rats were divided into three groups. Group 1 consisted of intact animals. Group 2 consisted of rats that had undergone parathyroidectomy. Group 3 consisted of rats that had undergone parathyroidectomy and were infused with 18.0 mmol/L phosphate solution (disodium phosphate to monosodium phosphate ratio of 4:1). Each group was further divided into two subgroups: one subgroup received 2.8 μg/mL aluminum solution for 3 hours, and the other subgroup received normal saline (control group). Glomerular filtration rate, urine flow rate, phosphate excretion fraction, plasma calcium, sodium, phosphate concentrations, blood pH, and urinary cyclic adenosine monophosphate (cAMP) levels were measured at selected time points. Aluminum concentrations in liver, kidney, and brain tissues were measured at selected time points. In intact animals, phosphate excretion fraction significantly increased 3 hours after aluminum infusion. Plasma calcium and phosphate concentrations decreased. In parathyroidectomized animals, phosphate excretion increased 3 hours after aluminum infusion, while animals receiving concurrent phosphate infusion also showed increased phosphate excretion at 2 and 3 hours. Urinary cyclic adenosine monophosphate (cAMP) concentrations in parathyroidectomized rats receiving phosphate infusion did not change significantly. Glomerular filtration rate, urine flow rate, and plasma sodium concentrations also did not change significantly. Blood pH values were not significantly different between the saline and aluminum infusion groups. Aluminum concentrations in the brain and kidneys were not significantly affected by aluminum infusion. Liver aluminum concentrations were not significantly increased in any of the aluminum-infused animals. The authors conclude that aluminum infusion inhibits renal phosphate reabsorption through a mechanism that does not involve parathyroid hormone, blood pH, or cAMP. Oral administration is safer, but serum electrolyte levels and renal function must be closely monitored. Nausea, vomiting, and diarrhea may occur and may be dose-related. Concomitant use of antacids containing aluminum and/or magnesium should be avoided, as they may bind to phosphates and prevent their absorption (calcium antacids may also bind to phosphates and are generally not used in patients with hypercalcemia). /Monophosphate or diphosphate sodium or potassium phosphate/

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Non-human toxicity values
Rat intramuscular LD50: 250 mg/kg
Rat oral LD50: 8290 mg/kg
Mouse oral LD50: >2000 mg/kg body weight
Rabbit dermal LD50: >7940 mg/kg body weight

[1]. Investigations on solute–solvent interactions of amino acids in aqueous solutions of sodium dihydrogen phosphate at different temperatures. Monatshefte für Chemie-Chemical Monthly, 2014, 145: 1063-1082.

Sodium dihydrogen phosphate is a type of sodium phosphate. Sodium phosphate is a saline laxative whose mechanism of action is believed to be increasing the amount of fluid in the small intestine. It usually induces defecation within 30 minutes to 6 hours after administration. See also: Sodium phosphate (note moved to).

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Drug Indications
For the treatment of constipation or for bowel cleansing prior to colonoscopy.
FDA LabelMechanism of Action
The mechanism of action of sodium phosphate is believed to be increasing the solute content in the intestinal lumen, thereby creating an osmotic gradient that draws water into the intestinal lumen.
...It promotes defecation by retaining water in the intestinal lumen through osmosis. ...It may also act by stimulating the release of cholecystokinin. /Sodium phosphate and disodium hydrogen phosphate (Fleet's Enema and Fleet's Sodium Phosphate)/
Phosphorus exists in the body in the form of organic and inorganic phosphates, has a variety of important biochemical functions, and participates in many important metabolic and enzymatic reactions in almost all organs and tissues. It regulates calcium homeostasis, buffers acid-base balance, and plays a major role in renal excretion of hydrogen ions.

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Therapeutic Use
Visicol tablets are indicated for colon cleansing in adults 18 years of age and older prior to colonoscopy. /Included in the US product label; Sodium dihydrogen phosphate (monohydrate) and disodium hydrogen phosphate (anhydrous)/
To determine whether adequate phosphate supplementation shortly after birth could prevent rickets in very low birth weight infants with prenatal phosphate deficiency, researchers studied 40 newborns. The initial dose was 50 mg of phosphate daily, administered as a mixture of 189 g of disodium hydrogen phosphate (disodium dihydrogen phosphate) and 82 g of sodium dihydrogen phosphate (sodium dihydrogen phosphate), diluted to 2 liters with a single-concentration chloroform solution. The control group received a placebo (single-concentration chloroform solution). If plasma phosphate concentrations remained below 1.5 mmol/L after one week, the supplementation dose was increased to 37.5 mg every 12 hours. Results showed that none of the infants receiving phosphate supplementation showed radiographic evidence of rickets, while 42% of the infants in the control group showed significant skeletal changes. The study concluded that prenatal phosphate deficiency due to placental insufficiency can be corrected by phosphate supplementation, thereby preventing rickets in preterm infants. This study aimed to evaluate the safety and efficacy of intravenous infusion of 0.15 mmol/kg phosphate (in sodium or potassium phosphate form, over 120 minutes) for the treatment of severe hypophosphatemia in adults. Severe hypophosphatemia was defined as a serum phosphate concentration below 1.5 mg/dL. Exclusion criteria were renal impairment and hypercalcemia. Patient assessment indicators included mental status, heart rate, and blood pressure. Serum phosphate sampling time after infusion was determined by the physician. This study included 6 men and 4 women. Only the study dose of phosphate was administered during the study period. No adverse events related to phosphate administration occurred. One patient receiving potassium phosphate experienced an increase in serum potassium level (5.2 mEq) after infusion. Serum phosphate levels were mean above the study criteria for severe hypophosphatemia in all ten patients, although nine of them also received oral phosphate supplementation. The dosage of intravenous sodium or potassium phosphate for treating severe hypophosphatemia was empirical. Previous toxicity evidence led to a lower recommended dose and slower administration. These data suggest that moderate doses of phosphate infusion over two hours are safe for adult patients, with safety assessed by patient mental status, vital signs, and blood biochemistry. Sixty patients were randomized to three groups of twenty each. Each group received one of the following solutions for bowel preparation: 10% mannitol, sodium picosulfate, or sodium phosphate. Parameters assessed included taste, tolerability, associated side effects, and cleansing effect. Orthostatic blood pressure and pulse, as well as serum sodium, potassium, calcium, and phosphate levels, were compared. …Sodium phosphate and 10% mannitol solutions were more effective for colon cleansing than sodium picosulfate solution… For more complete data on the therapeutic uses of sodium dihydrogen phosphate (9 types), please visit the HSDB record page.
Drug Warning
/Black Box Warning/ Rare but serious cases of acute phosphate nephropathy have been reported in patients who took oral sodium phosphate products for bowel preparation prior to colonoscopy. Some cases resulted in permanent kidney damage, and some patients required long-term dialysis. While some cases have occurred in patients without clear risk factors, high-risk groups for acute phosphate nephropathy may include: advanced age, hypovolemia, prolonged intestinal transit time (e.g., intestinal obstruction), active colitis, or pre-existing kidney disease, as well as patients taking medications that affect renal perfusion or function (e.g., diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]).
The U.S. Food and Drug Administration (FDA) has noted several reports of acute phosphate nephropathy (a type of acute kidney injury) associated with bowel preparation using oral sodium phosphate products (OSP) prior to colonoscopy or other procedures. These products include prescription drugs Visicol and OsmoPrep, as well as over-the-counter laxatives (such as Fleet Phospho-soda) available without a prescription. In some cases, these serious adverse events have occurred when patients used oral rehydration salts (OSP) for bowel cleansing, even though these patients had no identifiable risk factors for acute kidney injury. However, we cannot rule out the possibility that some patients were already dehydrated before taking OSP or did not replenish adequate fluids after taking it. Acute phosphate nephropathy is an acute kidney injury associated with the deposition of calcium phosphate crystals in the renal tubules, which can lead to permanent kidney damage. Acute phosphate nephropathy is a rare but serious adverse event associated with OSP use. These events were previously described in a Healthcare Practitioner Information Manual published by the U.S. Food and Drug Administration (FDA) in May 2006 and in a scientific document. Since the publication of these documents, the FDA has received more reports of acute phosphate nephropathy cases, and related descriptions have appeared in the literature. The risk of acute phosphate nephropathy may be increased in the following populations after using oral rehydration salts (OSP): those over 55 years of age; those with hypovolemia or reduced intravascular blood volume; those with underlying kidney disease, bowel obstruction, or active colitis; and those taking medications that affect renal perfusion or function (e.g., diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]). In light of the new safety information received, the FDA has requested that the manufacturers of two prescription drugs—Visicol and OsmoPrep—add a boxed warning to their product labels. The FDA has also required manufacturers to develop and implement risk assessment and mitigation strategies (REMS), including medication guidelines, to ensure that the benefits of these products outweigh the risks of acute phosphate nephropathy, and to conduct post-marketing clinical trials to further assess the risk of acute kidney injury from using these products. /Sodium dihydrogen phosphate monohydrate and disodium hydrogen phosphate anhydrous/
Sodium phosphate and 10% mannitol solution are more effective for colon cleansing than picosulfate solution. Serum electrolytes assessed showed significant changes in all three groups, but no significant clinical symptoms were observed. Elevated serum phosphate levels were the most significant change in patients who underwent bowel preparation with sodium phosphate solution, again without clinical symptoms. Changes in blood pressure and pulse suggested a reduction in intravascular volume, but no clinical symptoms were observed. Fifteen male subjects received 50 ml of a commercially available laxative containing 24 g of sodium dihydrogen phosphate (Sodium dihydrogen phosphate) and 6 g of disodium hydrogen phosphate (Disodium hydrogen phosphate; I) (containing 7 g of elemental phosphorus), taken with 500 ml of water; another eleven patients received 300 ml of magnesium citrate (II) solution containing 3.2 g of elemental magnesium. Patients ranged in age from 26 to 86 years. Serum magnesium, calcium, phosphorus, total protein, and albumin levels were measured at various time intervals before and within 16 hours of laxative administration, and before radiological examinations. Administration of a standard dose of I to healthy subjects before a barium enema resulted in a significant increase in serum phosphorus levels in all subjects, followed by a decrease in serum calcium levels. Compared to the control group who underwent the same examination, all indicators in the subjects showed significant changes. Serum potassium levels were significantly decreased, but serum sodium, chloride, bicarbonate, and magnesium levels did not show significant changes. Therefore, phosphate-containing laxatives should be used with caution in patients with severe renal insufficiency, hypocalcemia, or seizure disorders. Serum calcium levels should be closely monitored in patients requiring frequent re-administration due to bowel difficulties (e.g., patients undergoing radiological examinations). /Sodium dihydrogen phosphate monohydrate and anhydrous disodium hydrogen phosphate/
For more complete data on drug warnings for sodium dihydrogen phosphate (39 in total), please visit the HSDB record page.

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Pharmacodynamics
Sodium phosphate increases fecal water content, thereby promoting fecal peristalsis in the large intestine.

H2NAO4P

119.98

119.958

7558-80-7

Sodium dihydrogen phosphate monohydrate;10049-21-5;Phosphoric acid (sodium hydrate),≥99.0%;13472-35-0

23672064

Colorless, monoclinic crystals
White crystalline powder

1.40 g/mL at 20 °C

100°C

<0ºC

2

4

0

6

61.9

0

P(=O)(O[H])(O[H])[O-].[Na+]

AJPJDKMHJJGVTQ-UHFFFAOYSA-M

InChI=1S/Na.H3O4P/c;1-5(2,3)4/h;(H3,1,2,3,4)/q+1;/p-1

sodium;dihydrogen phosphate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

H2O: 100 mg/mL (833.47 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.)