Absorption, Distribution and Excretion
Potassium is a normal dietary component. Under steady-state conditions, the amount of potassium absorbed by the gastrointestinal tract equals the amount excreted in urine. Potassium deficiency occurs when the amount of potassium excreted by the kidneys and/or gastrointestinal tract exceeds the amount ingested. Under steady-state conditions, the continuous excretion of potassium chloride in urine and feces equals the daily intake. Orally and intravenously administered potassium chloride reaches equilibrium between extracellular and intracellular fluids. Almost all orally ingested potassium chloride is absorbed. The peak plasma concentration and its timing after ingestion depend on the formulation. Approximately 90% of ingested potassium doses are absorbed via passive diffusion through the upper small intestine membrane. Potassium is distributed throughout all tissues and is the main intracellular cation. Insulin, acid-base balance, aldosterone, and adrenergic activity regulate cellular potassium uptake. /Potassium/
For more complete data on the absorption, distribution, and excretion of potassium chloride (8 types), please visit the HSDB records page.

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Metabolism/Metabolites
Excretion pathway: Potassium is a normal dietary component. Under steady-state conditions, the amount of potassium absorbed by the gastrointestinal tract equals the amount excreted in urine. Potassium depletion occurs when the rate of potassium excretion by the kidneys and/or the rate of potassium excretion by the gastrointestinal tract exceeds the rate of potassium intake.

Toxicity Summary
Identification and Uses: Potassium chloride (KCl) is an odorless white crystal, crystalline powder, white granular powder, or colorless crystal with a strong salty taste. Currently, potassium chloride is not registered as a pesticide in the United States, but approved pesticide uses may change periodically; therefore, it is essential to consult federal, state, and local authorities for currently approved uses. Potassium chloride is used to prevent and treat potassium deficiency, for example, when using thiazide diuretics or corticosteroids to treat excessive vomiting or diarrhea, or when the diet is low in potassium; to treat cumulative digitalis poisoning; and as an ingredient in lethal injection. It is also used as a potash fertilizer in the fertilizer industry and in photographic buffer solutions. Potassium chloride has been shown to be used as a clay stabilizer in hydraulic fracturing. Human Exposure and Toxicity: Potassium chloride is an essential component of the human body for maintaining intracellular osmotic pressure and buffering, cell permeability, acid-base balance, muscle contraction, and nerve function. Acute oral poisoning is rare in humans because a single large dose usually only causes nausea and vomiting, and potassium chloride is rapidly excreted in the absence of prior kidney damage. Symptoms of acute potassium chloride poisoning are usually mild. Oral overdose can manifest as neuromuscular symptoms, including hyperkalemia, generalized muscle weakness and ascending paralysis, lethargy, dizziness, confusion, hypotension, acute cardiovascular changes with ECG abnormalities, and cardiac conduction block. Gastrointestinal symptoms include nausea, vomiting, paralytic ileus, and local mucosal necrosis, the latter potentially leading to intestinal perforation. Several cases of accidental intravenous or intraperitoneal injection of potassium chloride have been reported. Acute poisoning following parenteral administration presents with symptoms similar to oral poisoning, but develops more rapidly and is more severe. One case report of subcutaneous potassium chloride injection showed chemical burns and skin damage. In one routine spinal anesthesia, a mixture of 15 mL of 15% (30 mM) potassium chloride solution and bupivacaine was injected epidurally, resulting in permanent paraplegia. In another incident, a potassium chloride ampoule, instead of a bupivacaine ampoule, was mistakenly opened and accidentally injected intrathecally into a patient, causing pain, convulsions, and death within 2.5 hours post-injection. The usual therapeutic dose of oral potassium solution for adults is 1.5–3 g/day for preventing potassium loss; the dose for potassium supplementation is 3–7.5 g/day. When potassium chloride aqueous solution comes into contact with the skin of human volunteers, 60% concentrations were observed to cause skin irritation. When potassium chloride solution is applied to broken skin, the irritation threshold concentration is 5%. Oral potassium chloride (KCl) at a dose of approximately 31 mg/kg body weight/day has been reported to cause gastrointestinal irritation in humans. An epidemiological survey of potash miners showed that underground miners were not susceptible to any of the assessed diseases, including lung cancer. Animal studies: In a two-year study, no treatment-related carcinogenicity was observed in rats after ingesting potassium chloride at doses up to 1820 mg/kg body weight/day via food. A developmental study showed no fetal toxicity or teratogenicity at potassium chloride doses up to 235 mg/kg/day (mice) and 310 mg/kg/day (rats). No gene mutations were detected in bacterial assays (with or without metabolic activation). However, high concentrations of potassium chloride showed positive results in genotoxicity screening assays in various mammalian cell cultures. The role of potassium chloride in cell culture appears to be an indirect effect related to osmotic pressure and increased concentration. Ecotoxicity studies: Short-term acute toxicity tests on fish, water fleas, and algae yielded the following results (lowest tested values): 48-hour LC50 for channel catfish (Ictalurus punctulus) = 720 mg/L; 48-hour LC50 for Daphnia magna = 177 mg/L; 120-hour EC50 for Nitzschia linearis = 1337 mg/L. Chronic reproductive toxicity tests on the invertebrate Daphnia magna showed a lowest observed effect concentration (LOEC) of 101 mg/L. All collected acute and chronic aquatic toxicity study results were greater than 100 mg/L. Therefore, it can be concluded that potassium chloride is harmless to freshwater organisms.
Supplementation with high-potassium foods or potassium chloride may help restore normal potassium levels.
Interactions
Background and Objectives: We evaluated the effects of propofol and its interaction with potassium ion channels on isolated human umbilical vessels. Methods: Umbilical vascular rings were suspended in an ex vivo organ bath containing Klöninger's solution. In the first set of experiments, we examined the effect of propofol (10⁻⁹–10⁻⁴ M) on umbilical vessels pre-constricted with potassium chloride (60 mmol) in a concentration-dependent manner. In the second set of experiments, we investigated these effects in the presence of tetraethylammonium. Results: Low doses of propofol induced mild constriction in both pre-constricted umbilical artery and vein segments. 10⁻⁴ M propofol significantly dilated both the umbilical artery and vein. The addition of 10⁻¹ M tetraethylammonium significantly reduced this dilatory response. Conclusion: These results indicate that the response of propofol to KCl-induced umbilical artery and vein constriction is dose-dependent and involves Ca²⁺-activated K⁺ channels.
The nature of KCl-induced relaxation of the rat anal-coccygeal muscle was investigated. 2. Other K⁺ salts can mimic this relaxation effect, but NaCl cannot. 3. Muscles are more sensitive to the relaxation effect of KCl than to its contraction effect. 4. The addition of ouabain (100 μM) had no effect on the relaxation effect. 5. Tetrodotoxin (5 μg/mL), procaine (500 μM), and transection of inhibitory nerves all eliminated this relaxation effect. 6. The results indicate that the KCl-induced relaxation effect is due to K⁺ stimulation of inhibitory nerves.
This study used 12 male mongrel dogs; 6 were untreated (control group), and the other 6 received intravenous injections of furosemide (1 mg/kg) daily for 7 consecutive days prior to each study. Each animal received an intravenous injection of KCl at rates of 0.8, 1.6, or 3.2 mmol/kg/hr for 1 hour, but only once per study, with at least a 7-day interval between studies. All animals were intubated with thiopental sodium and mechanically ventilated to maintain PaCO2 at 4.0–4.5 kPa (30–35 torr), and anesthetized with nitrous oxide-oxygen and halothane. Daily administration of furosemide reduced serum potassium concentration from 4.48 mmol/L to 4.09 mmol/L, while serum sodium concentration remained unchanged. At intravenous administration of non-lethal doses of KCl at rates of 0.8 and 1.6 mmol/kg/hr, the furosemide pretreatment group had a higher incidence of arrhythmias (6 vs 3). The furosemide pretreatment group was more likely to die at lower serum potassium concentrations (12.2 vs 13.8 mmol/L, P<0.05), and cardiac arrest or ventricular fibrillation occurred earlier after intravenous administration of KCl at a rate of 3.2 mmol/kg/hr (44 vs 54 min, P<0.05). When serum potassium concentrations were 6.9–9.1 mmol/L, cardiac output, heart rate, and mean arterial pressure significantly increased, while stroke volume and peripheral resistance showed no statistically significant changes. When the same dose of KCl was infused, there was no significant difference in urinary potassium excretion between the untreated and treated groups. These data suggest that acute infusion of potassium chloride in furosemide-pretreated dogs may not be an effective treatment for hypokalemia and may be dangerous. This study investigated the effects of subcutaneous injection of deoxycorticosterone acetate (DOCA) combined with oral administration of sodium chloride solution on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric cancer in Wistar rats, and the effect of oral potassium supplementation on the enhanced gastric cancer development in DOCA-NaCl rats. After 25 weeks of oral treatment with the carcinogen, rats were subcutaneously injected with DOCA (50 mg/kg) twice weekly and given 1% sodium chloride solution (containing or without 1% potassium chloride) as drinking water. At week 52, the blood pressure, gastric cancer incidence, and number of tumors per rat in the DOCA-NaCl group were significantly higher than those in the untreated group. Long-term oral potassium supplementation in DOCA-NaCl hypertensive rats significantly reduced their blood pressure, gastric cancer incidence, and number of gastric cancers per rat. All gastric tumors were located in the gastric glandular region. Compared with the untreated group, DOCA-NaCl hypertensive rats showed significantly increased norepinephrine concentrations in the gastric wall and gastric mucosal marker indices, but oral potassium supplementation significantly reduced these levels. Therefore, administration of DOCA and NaCl can increase norepinephrine concentrations in the gastric wall and promote gastric cancer development, while oral potassium supplementation can reduce norepinephrine concentrations in the gastric wall of rats with gastric cancer. Since norepinephrine concentration has been used as a marker of sympathetic nervous system activity, these findings suggest that the sympathetic nervous system plays an important role in gastric cancer development and may be related to the proliferation of gastric antral epithelial cells. For more complete data on interactions of potassium chloride (20 in total), please visit the HSDB record page.

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Non-human toxicity values
Guinea pig oral LD50: 2500 mg/kg body weight
Mouse intravenous LD50: 117 mg/kg
Rat intravenous LD50: 39 mg/kg
Mouse oral LD50: 383 mg/kg
For more complete data on non-human toxicity of potassium chloride (9 in 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 is a white, colorless cubic crystal with a salty taste. (NTP, 1992)
Potassium chloride is a metallic chloride with the counterion K⁺. It is a fertilizer. It is a potassium salt, an inorganic chloride, and an inorganic potassium salt.
Potassium chloride is a white crystal or crystalline powder used as an electrolyte supplement, for treating hypokalemia, in buffer solutions, fertilizers, and explosives. The U.S. Food and Drug Administration (FDA) has revoked approval for all solid oral preparations containing potassium chloride that provide 100 mg or more of potassium per dose unit, except for extended-release preparations and preparations that are reconstituted into a solution before administration.
Potassium chloride is a metal halide composed of potassium and chloride. Potassium maintains intracellular tension and is essential for nerve conduction, myocardial, skeletal, and smooth muscle contraction, energy production, nucleic acid synthesis, maintaining blood pressure, and normal kidney function. This drug has the potential to lower blood pressure and may prevent hypokalemia when taken as a nutritional supplement. Potassium chloride sustained-release tablets are a sustained-release (ER) formulation whose main ingredient is potassium chloride, a metal halide salt composed of potassium and chlorine, used to treat and prevent hypokalemia. Oral administration of potassium chloride replenishes potassium. Potassium maintains normal fluid and electrolyte balance, regulates normal heart and muscle contraction function, and supports healthy bone density and blood pressure. It also plays an important role in nerve impulse transmission and energy production. Potassium salts are minerals. Potassium salts are minerals with the chemical formula KCl. The symbol of the International Mineralogical Association (IMA) is Syl. A white crystalline or crystalline powder used as an electrolyte supplement, a treatment for hypokalemia, a component of buffer solutions, and a component of fertilizers and explosives. A white crystalline or crystalline powder used in buffers, fertilizers, and explosives. It can be used to replenish electrolytes, restore electrolyte balance, and thus treat hypokalemia. See also: glucose; potassium chloride; sodium chloride (component); chloride ion (active moiety); potassium ion (active moiety)... See more...

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Drug Indications
For electrolyte supplementation and treatment of hypokalemia.
FDA Label

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Mechanism of Action
Potassium supplementation, such as consuming high-potassium foods or taking potassium chloride, may help restore normal potassium levels.
Potassium ions (K+) are the primary cations that maintain osmotic pressure balance in body fluids. In animals, maintaining normal cell volume and pressure depends on the pumping of sodium ions (Na+) and potassium ions (K+). K+/Na+ separation has allowed the evolution of reversible transmembrane potentials, which are crucial for nerve and muscle activity in animals. Potassium and chloride both play important roles in the transmission of nerve impulses to muscle fibers. /postasium/
The mutagenic effects of potassium chloride have been reported, likely due to its disruption of cellular osmotic balance, which in turn interferes with chromosome stability. This can lead to chromosome breakage (DNA breakage and chromosome structural instability) because potassium ions chelate magnesium ions, which are necessary to maintain chromatin integrity. Other chemicals may also produce similar effects (e.g., sodium chloride, sucrose). Potassium and chloride also play important roles in regulating the body's acid-base balance. Potassium is the main base in blood cells, and chloride maintains the electrochemical balance of carbon dioxide transport in red blood cells through anion exchange with bicarbonate ions (chloride transfer).
Therapeutic Use
This study determined the required oral dose of 10% potassium chloride to reverse hypokalemia induced by thiazide diuretics in 15 patients with essential hypertension taking Estrix (hydrochlorothiazide) 50 mg twice daily. During treatment with 50 mg hydrochlorothiazide twice daily, each patient achieved a serum potassium concentration at least 0.5 meq/L lower than two control values (mean reduction of 0.62 meq/L) for at least 2 months. The total daily dose of 10% potassium chloride oral solution was 40 mg, increased to 60 mg, 80 mg, and 100 mg every two months. During maintenance of thiazide administration, serum potassium levels recovered to 75% in 12 of the 15 patients. Eight of these patients received 40 mg of potassium chloride daily, and four received 60 mg daily. For patients with hypokalemia caused by thiazide drugs, a 60 mg dose is recommended. A 12-week open-label study enrolled 36 adult patients with cardiovascular disease to evaluate the efficacy, safety, and patient acceptability of daily 1.8 g extended-release potassium chloride tablets (Klotrix; I). These patients were receiving potassium-depleting diuretics for hypertension or atherosclerotic heart disease and were also taking oral potassium supplements. On day one of the study, the previous oral potassium supplement was discontinued, and I was introduced. After switching from the previous supplement to I, serum potassium levels remained normal, and other laboratory parameters did not change significantly. However, the incidence of side effects with I was low; more than half of the patients reported an unpleasant taste or aftertaste with the previous supplement, while no such cases occurred with I. Patient acceptance of I is high; 87% of patients who completed the study indicated a preference for I over their previous oral potassium supplements.
Medicinal (Veterinary): Available as an oral or parenteral potassium source… In cattle, it has been successfully used intravenously in “finishing cattle”… and for the treatment of severe diarrhea. Adding 1% potassium to feed reduces the incidence of urinary calculi in lambs, orally… for… finishing calves… as an electrolyte source.
Potassium chloride can be used to alleviate symptoms of hypokalemic periodic paralysis and Meniere's disease. Daily potassium intake reduces the risk of stroke-related death.
For more complete data on the therapeutic uses of potassium chloride (16 in total), please visit the HSDB record page.
Drug Warnings
The cardiac effects of hyperkalemia are the main toxic effects of potassium. These effects are mediated by alterations in the intracellular/extracellular potassium ion ratio, thereby altering cardiac conduction. In the absence of underlying conduction defects, transient cardiac conduction enhancement occurs when potassium concentrations exceed 7 mmol/L; however, severe cardiac conduction inhibition occurs when concentrations exceed 8.0 mmol/L. One effect of hyperkalemia is myocardial depolarization, thereby interfering with normal contractile function. Potassium chloride has a direct irritant effect on the gastrointestinal mucosa. Subcutaneous injection may cause local pain and inflammation. Skin rashes following potassium preparations are rarely reported. Initial symptoms of poisoning are usually gastrointestinal: nausea, vomiting, and diarrhea. These symptoms can develop into abdominal pain, eventually leading to paralytic ileus. Gastrointestinal perforation may occur after oral administration. Bleeding and perforation have been reported in patients who have taken solid potassium chloride. When serum potassium concentrations reach 7.0 mmol/L or higher, a variety of neuromuscular symptoms usually occur. General weakness and flaccid paralysis precede ascending paralysis. Tremor, paresthesia, decreased vibration and proprioception may be observed, but sensory function is usually intact. Dysarthria and dysphagia may occur. For more complete data on drug warnings (8 in total) regarding potassium chloride, please visit the HSDB record page.

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Pharmacodynamics
Potassium ions are the main intracellular cation in most human tissues. Potassium ions participate in many important physiological processes, including maintaining intracellular tone, transmitting nerve impulses, contraction of cardiac, skeletal, and smooth muscles, and maintaining normal kidney function. Intracellular potassium concentration is approximately 150 to 160 mEq/L. Normal adult plasma potassium concentration is 3.5 to 5 mEq/L. Active ion transport systems maintain the potassium concentration gradient across the plasma membrane. Potassium is a normal dietary component; under steady-state conditions, the amount of potassium absorbed from the gastrointestinal tract equals the amount excreted in urine. The normal dietary intake of potassium is 50 to 100 milliequivalents per day. Potassium deficiency occurs when the rate of renal excretion and/or gastrointestinal loss of potassium exceeds the rate of potassium intake. This type of potassium deficiency is usually caused by the use of diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or insufficient potassium supplementation in patients on long-term parenteral nutrition. Severe diarrhea, especially with vomiting, can rapidly lead to potassium deficiency. Potassium deficiency from these causes is often accompanied by chloride loss, manifesting as hypokalemia and metabolic alkalosis. Potassium deficiency can cause weakness, fatigue, arrhythmias (primarily ectopic beats), prominent U waves on the electrocardiogram, and in severe cases, even flaccid paralysis and/or impaired urine concentrating ability. If potassium deficiency caused by metabolic alkalosis cannot be controlled by correcting the underlying cause (e.g., the patient requires long-term diuretic use), supplementation with a high-potassium diet or potassium chloride may help restore normal potassium levels. In rare cases (e.g., patients with renal tubular acidosis), potassium deficiency may be accompanied by metabolic acidosis and hyperchloremia. For such patients, potassium supplementation should be performed using potassium salts other than potassium 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.)