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
Tmax for phosphate absorption with orally administered liquid sodium phosphate is 1-3h.
... Phosphates are slowly and incompletely absorbed ... . /Dibasic and monobasic sodium phosphate/
Intravenously infused phosphorus not taken up by the tissues is excreted almost entirely in the urine. Plasma phosphorus is believed to be filterable by the renal glomeruli, and the major portion of filtered phosphorus (greater than 80%) is actively reabsorbed by the tubules. Many modifying influences tend to alter the amount excreted in the urine.
An open-label pharmacokinetic study of Visicol in healthy volunteers was performed to determine the concentration-time profile of serum inorganic phosphorus levels after Visicol administration. All subjects received a total of 60 grams of sodium phosphate with a total liquid volume of 3.6 quarts. Subjects received a 30 gram dose (20 tablets given as 3 tablets every 15 minutes with 8 ounces of clear liquids) beginning at 6 PM and then received a second 30 gram dose (20 tablets given as 3 tablets every 15 minutes with 8 ounces of clear liquids) the following morning beginning at 6 AM. Twenty-three healthy subjects (mean age 57 years old; 57% male and 43% female; and 65% Hispanic, 30% Caucasian, and 4% African-American) participated in this pharmacokinetic study. The serum phosphorus level rose from a mean (+/- standard deviation) baseline of 4.0 (+/- 0.7) mg/dL to 7.7 (+/- 1.6 mg/dL), at a median of 3 hours after the administration of the first 30 gram dose of Visicol tablets The serum phosphorus level rose to a mean of 8.4 (+/- 1.9) mg/dL, at a median of 4 hours after the administration of the second 30 gram dose of Visicol tablets. The serum phosphorus level remained above baseline for a median of 24 hours after the administration of the initial dose of Visicol tablets (range 16 to 48 hours).

Toxicity Summary
IDENTIFICATION AND USE: 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 acidulant and sequestrant for foods. In addition, it is a buffering agent (electroplating baths); acidulant (processed meats, egg products, powdered drinks); builder (industrial cleaning formulations); metal phosphatizing reagent; mineral supplement; softening/conditioning agent (boiler water treatment); textile dyeing/printing auxiliary. In medicine, it is used as an enema solution. HUMAN EXPOSURE AND TOXICITY: Purposeful or accidental ingestion of more than the recommended dosage of tablets might be expected to lead to severe electrolyte disturbances, including hyperphosphatemia, hypocalcemia, hypernatremia, or hypokalemia, as well as dehydration and hypovolemia, with attendant signs and symptoms of these disturbances. Certain severe electrolyte disturbances may lead to cardiac arrhythmias, seizure, renal failure, and death. Prolongation of the QT interval has been observed in some patients who were dosed with Visicol tablets (sodium phosphate, monobasic, monohydrate and sodium phosphate, dibasic anhydrous). QT prolongation with Visicol tablets has been associated with electrolyte imbalances, such as hypokalemia and hypocalcemia. The estimated fatal dose of sodium phosphates is 50 g. Orally administered sodium phosphate-associated colonic mucosal abnormalities are infrequent but can mimic non-steroidal anti-inflammatory drug-induced injury or inflammatory bowel disease, and in particular must be differentiated from Crohn's disease. ANIMAL STUDIES: Doses of 250 g/kg by mouth produced diarrhea in rats, guinea pigs and rabbits. Six days of sodium dihydrogen phosphate treatment in rats consistently produced calcification of basement membranes of proximal tubules in the mid-cortex, followed by calcification of casts and basement membranes in the outer medulla and papilla after 10 days. Injection of 10.0 mg/chicken egg in air cell & yolk caused celosomia, exencephaly, microcephaly, brachygnathia, hyperplasia of heart, ablepharia, torticollis, microphthalmia, anophthalmia, coloma, ectromelia, phocomelia, buphthalmia, and cleft palate anomalies. In vitro mammalian chromosome aberration test in Chinese hamster lung fibroblasts without metabolic activation was negative. Study of the genotoxic potential of with the SOS chromatest in E. coli PQ37, PQ35 with and without metabolic activation was negative.

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Interactions
Sodium dihydrogen phosphate and sodium glycerophosphate inhibited intestinal calcium absorption in rats when administered simultaneously with 5-50 mmoles calcium chloride solution by gavage or in situ in ligatured jejunal loops.
The effects of sodium phosphate dibasic disodium phosphate buffer on in vivo release and on ocular and systemic absorption of timolol administered in matrices of monoisopropyl ester of polymethylvinyl ether/maleic anhydride ocularly to rabbits was studied; the vasoconstrictor phenylephrine methaoxedrine was added to some matrices to reduce the systemic absorption of timolol. The unbuffered matrix yielded a lower peak concentration of timolol in tear fluid and a lower steady-state concentration in plasma 3 hr later than the buffered one. Thus, sodium phosphate dibasic increases the rate of timolol release from the inserts several fold in tear fluid. Coadministration of phenylephrine in buffered matrices decreased the peak timolol concentration in plasma about 3 times and increased that in tear fluid about 2 fold. In iris-ciliary body, administration of buffered matrices resulted in timolol concentrations that were comparable with the levels after eye drop instillation. Compared to the unbuffered matrices, sodium phosphate dibasic, with or without phenylephrine, at least doubled the concentration ratio of iris-ciliary body to plasma.
The effect of aluminum on the renal handling of phosphate was studied in rats. Male Sprague Dawley rats were divided into 3 groups. The first group consisted of intact animals. The second consisted of rats that had been thyroparathyroidectomized. The third group consisted of thyroparathyroidectomized rats that were infused with 18.0 millimolar phosphate solution (disodium-phosphate monosodium-phosphate) ratio 4 to 1). Each group was subdivided into animals that were infused with 2.8 micrograms per milliliter aluminum for 3 hours or saline (controls). Glomerular filtration rate, urine flow rate, fractional excretion of phosphate, plasma calcium, sodium, and phosphate, blood pH, and urinary cyclic-adenosine-3',5'-monophosphate were measured at selected intervals. Liver, kidney, and brain aluminum concentrations were measured at selected times. In intact animals, fractional excretion of phosphate increased significantly after 3 hours of aluminum infusion. Plasma calcium and phosphate decreased. In the thyroparathyroidectomized animals, fractional excretion of phosphate increased after 3 hours of aluminum infusion and after 2 and 3 hours in animals that also received phosphates. Urinary cyclic-adenosine-3',5'- monophosphate concentrations were not significantly affected in thyroparathyroidectomized rats infused with phosphates. Glomerular filtration rate, urine flow rate, and plasma sodium were also not significantly affected. Blood pH was not significantly different between saline and aluminum infused rats in any group. Brain and kidney aluminum concentrations were not significantly affected by aluminum infusion. Liver aluminum concentrations were not significantly higher in all aluminum infused animals. The authors conclude that aluminum infusion inhibits renal phosphate reabsorption by a mechanism that does not involve parathyroid hormone, blood pH, or 3',5'-monophosphate.
Oral administration is safer, but careful monitoring of serum electrolyte levels and renal function is necessary. Nausea, vomiting, and diarrhea may occur and may be dose dependent. Concomitant use of antacids containing aluminum and/or magnesium should be avoided, because they may bind phosphate and prevent it absorption (calcium antacids also may bind phosphate, and it is assumed that these agents are not given to hypercalcemic patients). /Monobasic or dibasic sodium or potassium phosphate/

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Non-Human Toxicity Values
LD50 Rat intramuscular 250 mg/kg
LD50 Rat oral 8290 mg/kg
LD50 Mouse oral /greater than/ 2000 mg/kg bw.
LD50 Rabbit dermal /greater than/ 7940 mg/kg bw.

[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 dihydrogenphosphate is a sodium phosphate.
Sodium phosphate is a saline laxative that is thought to work by increasing fluid in the small intestine. It usually results in a bowel movement after 30 minutes to 6 hours.
See also: Sodium Phosphate (annotation moved to).

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Drug Indication
Used to treat constipation or to clean the bowel before a colonoscopy.
FDA Label

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Mechanism of Action
Sodium phosphate is thought to work by increasing the amount of solute present in the intestinal lumen thereby creating an osmotic gradient which draws water into the lumen.
... /Promotes/ defecation by retaining water in the intestinal lumen through osmotic forces. ... May also act by stimulating release of cholecystokinin. /Sodium phosphate & sodium biphosphate (Fleet's enema & Fleet's Phospho-soda)/
Phosphorus in the form of organic and inorganic phosphate has a variety of important biochemical functions in the body and is involved in many significant metabolic and enzyme reactions in almost all organs and tissues. It exerts a modifying influence on the steady state of calcium levels, a buffering effect on acid-base equilibrium and a primary role in the renal excretion of hydrogen ion.

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Therapeutic Uses
Visicol Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. /Included in US product label; sodium phosphate, monobasic, monohydrate and sodium phosphate, dibasic anhydrous/
To determine whether phosphate supplementation, started soon after birth in adequate quantity, would prevent rickets in very low birth weight infants with prenatal deficiency of phosphate, 40 neonates were given an initial dose of 50 mg/day of phosphate administered as a mixture of 189 g of sodium phosphate dibasic (disodium hydrogen phosphate) and 82 g of sodium phosphate monobasic (sodium dihydrogen phosphate) made up to 2 liters with single strength chloroform water or placebo (single strength chloroform water). Supplementation was increased to 37.5 mg every 12 hr if the plasma phosphate concentration remained less than 1.5 mmol/L after one wk. Results showed that no infant receiving phosphate supplements had radiological evidence of rickets whereas bone changes were apparent in 42% of the control group. It was concluded that prenatal deficiency of phosphate, due to placental insufficiency, can be corrected by phosphate supplementation, thereby preventing rickets of prematurity.
The objective of this study was to determine the safety and efficacy of 0.15 mmol/kg phosphorus (PHOS), administered intravenously as sodium or potassium phosphate over 120 minutes, in the treatment of adults suffering from severe hypophosphatemia. Severe hypophosphatemia was defined as a serum PHOS concentration of /LE/ 1.5 mg/dL. Exclusion criteria were renal impairment and hypercalcemia. Patient assessments included mental status, heart rate, and blood pressure. The timing of post-infusion serum PHOS sampling was at physician discretion. Six men and four women were enrolled in the study. During the study period, the only parenteral PHOS administered was the study dose. There were no patient adverse events associated with PHOS administration. One patient who received potassium phosphates had an elevated post-infusion serum potassium (5.2 mEq). Serum PHOS increased above the study criteria for severe hypophosphatemia in all ten patients, although nine patients received concomitant oral PHOS supplements. The dosing of intravenous sodium or potassium phosphate in the treatment of patients with severe hypophosphatemia is empiric. Historical evidence of toxicity has caused dosing recommendations to be low and slow. These data demonstrate the safety of a moderate PHOS dose when administered over two hours to adults, as measured by patient mental status, vital signs, and blood chemistry analysis.
Sixty patients were randomly divided into three groups of 20 each. Each group was submitted to a bowel preparation with one of the following solutions: 10% manitol, sodium picosulfate or sodium phosphate. The parameters evaluated were: taste, tolerance, associated side effects and quality of cleansing. Postural blood pressure and pulse rate as well as serum sodium, potassium, calcium and phosphate were compared. ... Sodium phosphate and 10% manitol solutions provided superior results in terms of colon cleansing compared to sodium picosulfate solution...
For more Therapeutic Uses (Complete) data for SODIUM DIHYDROGEN PHOSPHATE (9 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long-term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]).
FDA has become aware of reports of acute phosphate nephropathy, a type of acute kidney injury, associated with the use of oral sodium phosphate products (OSP) for bowel cleansing prior to colonoscopy or other procedures. These products include the prescription products, Visicol and OsmoPrep, and OSPs available over-the-counter without a prescription as laxatives (e.g., Fleet Phospho-soda). In some cases when used for bowel cleansing, these serious adverse events have occurred in patients without identifiable factors that would put them at risk for developing acute kidney injury. We cannot rule out, however, that some of these patients were dehydrated prior to ingestion of OSPs or they did not drink sufficient fluids after ingesting OSP. Acute phosphate nephropathy is a form of acute kidney injury that is associated with deposits of calcium-phosphate crystals in the renal tubules that may result in permanent renal function impairment. Acute phosphate nephropathy is a rare, serious adverse event that has been associated with the use of OSPs. The occurrence of these events was previously described in an Information for Healthcare Professionals sheet and an FDA Science Paper issued in May 2006. Additional cases of acute phosphate nephropathy have been reported to FDA and described in the literature since these were issued. Individuals who appear to have an increased risk of acute phosphate nephropathy following the use of OSPs include persons: who are over age 55; who are hypovolemic or have decreased intravascular volume; who have baseline kidney disease, bowel obstruction, or active colitis; and who are using medications that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]). As a result of new safety information received, FDA is requiring the manufacturer of Visicol and OsmoPrep, the two OSPs available by prescription only, to add a Boxed Warning to the labeling for these products. FDA is also requiring that the manufacturer develop and implement a risk evaluation and mitigation strategy (REMS), which will include a Medication Guide, to ensure that the benefits of these products outweigh the risk of acute phosphate nephropathy, and to conduct a postmarketing clinical trial to further assess the risk of acute kidney injury with use of these products. /Sodium phosphate, monobasic, monohydrate and sodium phosphate, dibasic anhydrous/
Sodium phosphate and 10% mannitol solutions provided superior results in terms of colon cleansing compared to sodium picosulfate solution. All serum electrolytes evaluated were significantly altered in the three groups, without important clinical signs. High levels of serum phosphate were the most striking alteration in patients prepared with sodium phosphate solution, again with no clinical signs. Variations related to blood pressure and pulse rate suggested contraction of intravascular volume, with no clinical effects.
Fifteen male subjects received 50 mL of commerical laxative containing 24 g of sodium biphosphate (sodium phosphate monobasic) and 6 g of sodium phosphate (sodium phosphate dibasic; I) (7 g of elemental phosphorus) administered with 500 mL of water and 11 patients received 300 mL of magnesium citrate (II) containing 3.2 g of elemental magnesium. Patients ranged in age from 26 to 86 yr. Serum magnesium, calcium, phosphorus, total protein, and albumin were determined before and at various intervals up to 16 hr after administration of the laxative and prior to radiological study. The administration of I in conventional doses to normal subjects prior to barium enema resulted in a striking increase in serum phosphorus levels followed by a decline in serum calcium levels in all subjects. Changes were highly significant when compared with control subjects who were prepared for the same procedure with II. Levels of serum potassium also decreased significantly but not serum sodium, chloride, bicarbonate, or magnesium. It would seem wise to caution against the use of phosphate containing laxatives in the presence of severe renal insufficiency, hypocalcemia, or convulsive disorders. In patients who are receiving frequent, repetitive dosages because of difficulty in cleansing the bowel for radiological procedures, serum calcium should be closely monitored. /Sodium phosphate, monobasic, monohydrate and sodium phosphate, dibasic anhydrous/
For more Drug Warnings (Complete) data for SODIUM DIHYDROGEN PHOSPHATE (39 total), please visit the HSDB record page.

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Pharmacodynamics
Sodium phosphate inceases fecal water content to increase mobility through 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.)