Absorption, Distribution and Excretion
Potassium is a normal dietary constituent and under steady-state conditions the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine.
Potassium is a normal dietary constituent and, under steady-state conditions, the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake.
At steady state continuous excretion of potassium chloride in the urine and faeces equals the daily intake.
Orally and intravenously administered potassium chloride reaches an equilibrium between the extracellular fluid and intracellular space.
Almost all orally administered potassium chloride is absorbed. The peak level and its occurrence time after ingestion depend on the preparation administered.
About 90% of the ingested dose of potassium is absorbed by passive diffusion in the membrane of the upper intestine. Potassium is distributed to all tissues where it is the principal intracellular cation. Insulin, acid-base status, aldosterone, and adrenergic activity regulate cellular uptake of potassium. /potassium/
For more Absorption, Distribution and Excretion (Complete) data for POTASSIUM CHLORIDE (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
Route of Elimination: Potassium is a normal dietary constituent and, under steady-state conditions, the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake.

Toxicity Summary
IDENTIFICATION AND USE: Potassium chloride (KCl) consists of odorless white crystals or crystalline powder or white granular powder or colorless crystals, with a strong saline taste. It is not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. KCl is used as prevention and treatment of potassium deficiency, e.g. when thiazide diuretics or corticosteroids are used in case of excessive vomiting or diarrhea, or diets poor in potassium; in the treatment of cumulative digitalis poisoning; and as a component of lethal injections. It is also used in the fertilizer industry as potash and in buffer solutions for photography. Potassium chloride has been identified as being used in hydraulic fracturing as a clay stabilizer. HUMAN EXPOSURE AND TOXICITY: KCl is an essential constituent of the body for intracellular osmotic pressure and buffering, cell permeability, acid-base balance, muscle contraction and nerve function. In humans, acute oral toxicity is rare because large single doses induce nausea and vomiting, and because KCl is rapidly excreted in the absence of any pre-existing kidney damage. Symptoms of acute poisoning after ingestion of potassium chloride are usually mild. KCl oral overdoses manifests in neuromuscular signs in the form of hyperkalemia, general muscular weakness and ascending paralysis, listlessness, vertigo, mental confusion, hypotension, acute cardiovascular changes with ECG abnormalities, and heart block. Gastrointestinal symptoms manifest as nausea, vomiting, paralytic ileus, and local mucosal necrosis, which may lead to perforation. There are several case reports of accidental iv or ip administrations of KCl. Symptoms of acute poisoning after parenteral administration are similar to symptoms after oral exposure but can appear more promptly and be more severe. A case report of a subcutaneous injection of KCl reports chemical burns and skin lesions. During routine spinal anesthesia, an injection of 15 mL of 15% KCl (30 mM) mixed with bupivacaine epidurally caused permanent parapalegia and an ampule of potassium chloride, instead of bupivacaine, was mistakenly opened and inadvertently administered intrathecally to a patient, resulting in pain, cramps, and death within 2.5 hours of injection. Usual therapeutic doses of potassium for oral solution-adults are 1.5-3 g/day to prevent depletion, and 3-7.5 g/day for replacement. A threshold concentration for skin irritancy of 60 % was seen when KCl in aqueous solution was in contact with skin of human volunteers. The threshold concentration when applied to broken skin was 5 %. Gastro-intestinal irritant effects in humans caused by KCl administrated orally have been reported at doses from about 31 mg/kg bw/day. One epidemiological investigation among potash miners disclosed no evidence of predisposition of underground miners to any of the diseases evaluated, including lung cancer. ANIMAL STUDIES: No evidence of treatment-related carcinogenicity was observed in rats administered up to 1820 mg KCl/kg body weight/day through the food in a 2 year study. A developmental study revealed no fetotoxic or teratogenic effects of KCl in doses up to 235 mg/kg/day (mice) and 310 mg/kg/day (rats). No gene mutations were reported in bacterial tests, with and without metabolic activation. However, high concentrations of KCl showed positive results in a range of genotoxic screening assays using mammalian cells in culture. The action of KCl in culture seems to be an indirect effect associated with an increased osmotic pressure and concentration. ECOTOXICITY STUDIES: In short-term acute toxicity tests with fish, daphnia and algae the following results were found (lowest test result values): Ictalurus punctulus 48hr-LC50 = 720 mg/L; Daphnia magna: 48h-LC50 = 177 mg/L; Nitzschia linearis: 120 h-EC50 = 1337 mg/L. A chronic reproductive test with the invertebrate Daphnia magna gave a LOEC of 101 mg/L. All the studies compiled on the acute and chronic aquatic toxicity were > 100 mg/L. Thus it is concluded that KCl is not hazardous to freshwater organisms.
Supplemental potassium in the form of high potassium food or potassium chloride may be able to restore normal potassium levels.

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Interactions
BACKGROUND AND OBJECTIVE: We have evaluated the effects of propofol and its relationship with K+ channels on human isolated umbilical vessels. METHODS: Umbilical vessel rings were suspended in isolated organ baths containing Krebs-Ringer solution. In the first series of experiments the effect of propofol (10(-9)-10(-4) M) was examined in a concentration-dependent manner on umbilical vessels precontracted with KCl (60 mmol). In the second series, these effects were studied in the presence of tetraethylammonium. RESULTS: A mild contraction was produced by low dose propofol in both precontracted umbilical artery and umbilical vein segments. 10(-4) M propofol caused significant relaxation in both umbilical artery and umbilical vein. The relaxation response was significantly reduced by the addition of 10(-1) M tetraethylammonium. CONCLUSION: These results suggested that the responses of propofol on KCl-induced contractions of both umbilical artery and vein were dose dependent, and this effect involved Ca2+ activated K+ channels.
The nature of KCl-induced relaxations of the rat anococcygeus muscle was investigated. 2. The relaxations were mimicked by other K+ salts, but not by NaCl. 3. The muscle was more susceptible to the relaxant effects of KCl than the contractile effects. 4. Addition of ouabain (100 micron) had no effect on the relaxations. 5. The relaxations were abolished by tetrodotoxin (5 microgram/mL), procaine (500 micron), and by section of the inhibitory nerves. 6. The results suggest that KCl-induced relaxations are due to stimulation of the inhibitory nerves by K+.
Twelve male mongrel dogs were used for this study; six were untreated (control) and six were given intravenous furosemide (1 mg/kg) daily for seven consecutive days before each study. Each animal received intravenous KCl 0.8, 1.6 or 3.2 mMol/kg/hr for one hour, but only one dose for each study and at least seven days were allowed between studies. The animals were given thiopentone for tracheal intubation and mechanically ventilated, maintaining a PaCO2 of 4.0 to 4.5 kPa (30-35 torr) and anaesthetized with nitrous oxide-oxygen and halothane. Daily administration of furosemide reduced serum potassium from 4.48 to 4.09 mMol/1 with no significant change in serum sodium. A greater number of furosemide-pretreated animals (6 vs 3) developed cardiac dysrhythmias during non-lethal intravenous KCl at 0.8, 1.6 mMol/kg/hr. The furosemide-pretreated group tended to succumb at a lower serum potassium concentration (12.2 vs 13.8 mMol/I, P less than 0.05) and developed earlier onset (44 vs 54 min, P less than 0.05) of cardiac standstill or ventricular fibrillation following intravenous KCl at 3.2 mMol/kg/hr. Cardiac output, heart rate and mean arterial pressure were significantly elevated during serum concentrations of 6.9-9.1 mMol/1, while no statistically significant changes were observed for stroke volume and peripheral resistance. There were no significant differences of urinary potassium excretion between the untreated and treated groups when like doses of KCl were infused. These data suggest that acute infusion of KCl in furosemide-pretreated dogs may not be an effective means of treating hypokalaemia and could be hazardous.
The effect of s.c. administration of deoxycorticosterone acetate (DOCA) plus p.o. treatment with NaCl solution on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and the effect of p.o. potassium supplementation on the enhanced induction of gastric carcinogenesis in DOCA-NaCl rats were investigated in Wistar rats. After 25 weeks of p.o. treatment with the carcinogen, rats received s.c. injections of DOCA (50 mg/kg) twice a week and were given 1% NaCl solution with and without 1% KCl as drinking water. In Week 52, the blood pressure, the incidence of gastric cancer, and the number of cancers per rat were significantly greater in DOCA-NaCl rats than in the untreated group. Prolonged p.o. treatment of DOCA-NaCl hypertensive rats with potassium significantly reduced their blood pressure, the incidence of gastric cancers, and their number per rat. All gastric tumors were in the glandular portions of the stomach. The norepinephrine concentration in the gastric wall and the labeling indices of gastric mucosa were significantly greater in DOCA-NaCl hypertensive rats than in the untreated group, but p.o. potassium supplementation significantly reduced the norepinephrine concentration in the gastric wall and the labeling indices of the gastric mucosa in DOCA-NaCl rats. Thus, administration of DOCA and NaCl increased the norepinephrine concentration in the gastric wall and promoted gastric carcinogenesis, and p.o. potassium supplementation decreased the norepinephrine concentration in the gastric rats. Inasmuch as the norepinephrine concentration has been used as a marker of sympathetic nervous activity, these findings suggest that the sympathetic nervous system plays an important role in gastric carcinogenesis, probably associated with cell proliferation of antral epithelial cells.
For more Interactions (Complete) data for POTASSIUM CHLORIDE (20 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Guinea pig oral 2500 mg/kg body weight
LD50 Mouse iv 117 mg/kg
LD50 Rat iv 39 mg/kg
LD50 Mouse oral 383 mg/kg
For more Non-Human Toxicity Values (Complete) data for POTASSIUM CHLORIDE (9 total), please visit the HSDB record page.

[1]. The inhibitory effects of potassium chloride versus potassium silicate application on (137)Cs uptake by rice. J Environ Radioact. 2016;153:188-194.

[2]. Saxena K. Clinical features and management of poisoning due to potassium chloride. Med Toxicol Adverse Drug Exp. 1989;4(6):429-443.

Potassium chloride appears as white colorless cubic crystals. Strong saline taste. (NTP, 1992)
Potassium chloride is a metal chloride salt with a K(+) counterion. It has a role as a fertilizer. It is a potassium salt, an inorganic chloride and an inorganic potassium salt.
A white crystal or crystalline powder used as an electrolyte replenisher, in the treatment of hypokalemia, in buffer solutions, and in fertilizers and explosives. The FDA withdrew its approval for the use of all solid oral dosage form drug products containing potassium chloride that supply 100 mg or more of potassium per dosage unit, except for controlled-release dosage forms and those products formulated for preparation of solution prior to ingestion.
Potassium Chloride is a metal halide composed of potassium and chloride. Potassium maintains intracellular tonicity, is required for nerve conduction, cardiac, skeletal and smooth muscle contraction, production of energy, the synthesis of nucleic acids, maintenance of blood pressure and normal renal function. This agent has potential antihypertensive effects and when taken as a nutritional supplement may prevent hypokalemia.
Potassium Chloride Extended-Release is an extended-release (ER) formulation of potassium chloride, the metal halide salt composed of potassium and chloride, that is used for the treatment and prophylaxis of hypokalemia. Upon oral administration, potassium chloride provides potassium. Potassium maintains normal fluid and electrolyte balance, regulates the proper functioning of heart and muscle contractions, supports healthy bone density and blood pressure. It also plays an important role in the transmission of nerve impulses and energy production.
sylvine is a mineral.
Sylvite is a mineral with formula of KCl. The IMA symbol is Syl.
A white crystal or crystalline powder used as an electrolyte replenisher, in the treatment of hypokalemia, in buffer solutions, and in fertilizers and explosives.
A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.
See also: Dextrose; potassium chloride; sodium chloride (component of); Chloride Ion (has active moiety); Potassium Cation (has active moiety) ... View More ...

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Drug Indication
For use as an electrolyte replenisher and in the treatment of hypokalemia.
FDA Label

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Mechanism of Action
Supplemental potassium in the form of high potassium food or potassium chloride may be able to restore normal potassium levels.
K+ is the principal cation mediating the osmotic balance of the body fluids. In animals, the maintenance of normal cell volume and pressure depends on Na+ and K+ pumping. The K+/Na+ separation has allowed for evolution of reversible transmembrane electrical potentials essential for nerve and muscle action in animals, and both potassium and chloride are important in transmission of nerve impulses to the muscle fibers. /postasium/
The reported mutagenic effect of KCl most probably results from a disruption of osmotic balance of cells with a subsequent interference with chromosomal stability. This may result in the clastogenic effects (DNA breakage and chromosome structural instability) due to K+ effects on sequestering of Mg2+ ions required for normal maintenance of chromatin integrity. Other chemicals may also exert such effect (e.g. NaCl, sucrose).
Potassium and chloride is also important in the regulation of the acid-base balance of the body. Potassium is the principal base in tissues of blood cells, and Cl maintains electrochemical neutrality by anion exchange with bicarbonate (the chloride shift) in the CO2 transport in the blood red cells.

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Therapeutic Uses
The oral dose of 10% potassium chloride elixir (Kay Ciel) required to reverse thiazide-induced hypokalemia was determined in 15 patients with essential hypertension who were taking Esidrix (hydrochlorothiazide) in a dose of 50 mg. twice daily. Each patient had maintained a serum potassium concentration of at least 0.5 meq./l. less than duplicate control values (mean decreases, 0.62 meq./l.) for at least 2 months during therapy with hydrochlorothiazide, 50 mg. twice daily. Potassium chloride 10% elixir was administered in a total daily dose of 40 mg. with bimonthly increments to 60 mg., 80 mg. and 100 mg. while the thiazide administration was maintained. The serum potassium deficit was repleted to 75% in 12 of the 15 patients. In 8 of the 12, this was accomplished with 40 mg. potassium chloride daily, and in 4, with 60 mg. daily. The latter dose is recommended in patients with thiazide-induced hypokalemia.
Thirty-six adult patients with cardiovascular disorders were enrolled in an open 12 week study to evaluate the efficacy, safety and patient acceptance of sustained-release potassium chloride (Klotrix; I) tablets, at a dosage of 1.8 g daily. These patients were on an established regimen of potassium wasting diuretics as part of their treatment for hypertension or arteriosclerotic heart disease, and all were receiving an oral potassium supplement. On the first day of the study, the previously used oral potassium supplement was discontinued and I substituted. Serum potassium levels remained normal and other laboratory parameters did not change significantly as a result of the changeover from the previous potassium supplement to I. However, side effects occurred less frequently with I, and while more than half the patients commented on the bad taste or bad aftertaste of their previous supplement, no such comments were recorded for I. Patient acceptance of I was high, and 87% of the patients who completed the study expressed a preference for I over their previous oral potassium supplement.
Medication (vet): as oral or parenteral source of potassium... in cattle it has been successfully used iv for "creeper cows"...& in cases of debilitating diarrhea. 1% Level in feed reduces incidence of urolithiasis in lambs, & orally...for...feeder calves...as electrolyle source.
Potassium chloride is of value for the relief of symptoms of hypokaliemic periodic paralysis, and the symptoms of Meniere's disease. Daily intake of potassium decreases the risk of stroke-associated mortality.
For more Therapeutic Uses (Complete) data for POTASSIUM CHLORIDE (16 total), please visit the HSDB record page.

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Drug Warnings
The cardiac effects of hyperkalemia are principal toxic effects of potassium. They are mediated through changes in the intra/extracellular potassium ratio, which alters cardiac conduction. With no underlying conduction defects a transient increase in cardiac conduction occurs with potassium concentrations above 7 mmol/L, but a profound depression occurs when concentrations rise over 8.0 mmol/L. One of the effects of hyperkalemia is the depolarisation of cardiac muscle, which interferes with normal contractility. Potassium chloride exerts a direct irritant effect on the gastrointestinal mucosa.
Local pain and inflammation may result from subcutaneous injection). Skin rash has rarely been reported with potassium preparations.
The initial signs of poisoning are generally gastrointestinal: nausea, vomiting and diarrhea. These symptoms can develop into abdominal pain and eventually paralytic ileus. Gastrointestinal perforation after oral exposure can occur. Bleeding and perforation have been reported in patients receiving solid forms of potassium chloride.
A number of neuromuscular effects can be seen, usually with potassium concentrations of 7.0 mmol/L or higher. General weakness and flaccidity precede ascending paralysis. Tremor, paresthesias, decreased vibration perception and proprioception can be seen, but the sensory function is usually intact. Dysarthria and dysphagia may occur.
For more Drug Warnings (Complete) data for POTASSIUM CHLORIDE (8 total), please visit the HSDB record page.

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Pharmacodynamics
The potassium ion is in the principle intracellular cation of most body tissues. Potassium ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity, the transmission of nerve impulses, the contraction of cardiac, skeletal and smooth muscle, and the maintenance of normal renal function. The intracellular concentration of potassium is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane. Potassium is a normal dietary constituent and under steady-state conditions the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of potassium is 50 to 100 mEq per day. Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primarily or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Potassium depletion may produce weakness, fatigue, disturbances of cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and, in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine. If potassium depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, e.g., where the patient requires long-term diuretic therapy, supplemental potassium in the form of high potassium food or potassium chloride may be able to restore normal potassium levels. In rare circumstances (e.g., patients with renal tubular acidosis) potassium depletion may be associated with metabolic acidosis and hyperchloremia. In such patients, potassium replacement should be accomplished with potassium salts other than the chloride, such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate.

CLK

74.5513

73.932

7447-40-7

4873

White to off-white solid powder

1.98 g/mL at 25 °C(lit.)

1420°C

770 °C(lit.)

1500°C

n20/D 1.334

0

1

0

2

2

0

WCUXLLCKKVVCTQ-UHFFFAOYSA-M

InChI=1S/ClH.K/h1H;/q;+1/p-1

potassium;chloride

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)

H2O : ~50 mg/mL (~670.69 mM)
DMSO : ~1 mg/mL (~13.41 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.)