D-Pantothenic acid sodium, a precursor to coenzyme A, plays a key role in energy production and lipid metabolism via the TCA cycle and β-oxidation pathways, respectively [1].

In mice, neural tube abnormalities caused by valproic acid (VPA; 300, 400, and 500 mg/kg, sc) are lessened by pantothenic acid (PTA; 3x10, 3x100, and 3x300 mg/kg)[2].

Animal/Disease Models: Female ICR mice weighing 29-35 g[2]
Doses: 3x10, 3x100, and 3x300 mg/kg (10 mL/kg, volume administered)
Route of Administration: Injected intraperitoneally (ip) on day 8.5 of gestation
Experimental Results: Dramatically decreased VPA (300, 400, and 500 mg/kg, sc)-induced exencephaly, while none of the other external malformations such as open eyelid or skeletal malformations such as fused, absent, or bifurcated ribs and fused thoracic vertebrae and fused sternebrae were decreased.

Absorption, Distribution and Excretion
Dietary pantothenic acid is primarily in the form of CoA or ACP and must be converted into free pantothenic acid for absorption. CoA and ACP are hydrolyzed into 4'-phosphopantetheine which is then dephosphorylated into pantetheine and subsequently hydrolyzed again to free pantothenic acid by Pantetheinase in the intestinal lumen. Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system with passive diffusion acting as a secondary pathway. As intake increases up to 10-fold absorption rate can decrease to as low as 10% due to transporter saturation.
Pantothenic acid is absorbed in the small intestine by active transport at low concentrations of the vitamin and by passive transport at higher concentrations. Because the active transport system is saturable, absorption is less efficient at higher concentrations of intake. However, the exact intake levels at which absorption decreases in humans are not known. Pantothenic acid is excreted in the urine in amounts that are proportional with dietary intake over a wide range of intake values.
Pantothenic acid is readily absorbed from the GI tract. It is present in all tissues, in concentrations ranging from 2-45 ug/g. Pantothenic acid apparently is not destroyed in human body since intake and excretion ... are approximately equal. About 70% of unchanged pantothenic acid is excreted in urine and about 30% in feces.
Pantothenic acid is readily absorbed from the GI tract following oral administration. Normal serum pantothenate concentrations are 100 ug/mL or greater. /Pantothenic acid/ is widely distributed into body tissues, mainly as coenzyme A. Highest concentrations are found in the liver, adrenal glands, heart, and kidneys. Milk of nursing mothers receiving a normal diet contains about 2 ug of pantothenic acid per mL. About 70% of an oral dose of pantothenic acid is excreted unchanged in urine and about 30% in feces.
... /N/ewborn pantothenic acid levels are significantly greater than maternal levels. At term, mean pantothenate levels in 174 mothers were 430 ng/mL (range 250-710) and in their newborns 780 ng/mL (range 400-1480). Placental transfer of pantothenate to the fetus is by active transport, but it is slower than transfer of other B complex vitamins. In one report, low-birth-weight infants had significantly lower levels of pantothenic acid than did normal weight infants.
For more Absorption, Distribution and Excretion (Complete) data for D-Pantothenic Acid (20 total), please visit the HSDB record page.

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Metabolism / Metabolites
The synthesis of Coenzyme A (CoA) from pantothenate is regulated primarily by pantothenate kinase, an enzyme that is inhibited by the pathway end products, CoA and acyl CoA.
/P/antothenic acid is required for intermediary metabolism of carbohydrates, proteins, and lipids. Pantothenic acid is a precursor of coenzyme A which is required for acetylation (acyl group activation) reactions in gluconeogenesis, in the release of energy from carbohydrates, the synthesis and degradation of fatty acids, and the synthesis of sterols and steroid hormones, porphyrins, acetylcholine, and other compounds.
Absorption Coenzyme A (CoA). CoA in the diet is hydrolyzed in the intestinal lumen to dephospho CoA, phosphopantetheine, and pantetheine, with the pantetheine subsequently hydrolyzed to pantothenic acid. Pantothenic acid was the only one of these pantothenate-containing compounds absorbed by rats in studies on absorption of the various forms. Absorption is by active transport at low concentrations of the vitamin and by passive transport at higher concentrations in animal models. Because the active transport system is saturable, absorption will be less efficient at higher concentrations of intake, but the intake levels at which absorptive efficiency decreases in humans are not known.
Intestinal microflora have been observed to synthesize pantothenic acid in mice, but the contribution of bacterial synthesis to body pantothenic acid levels or fecal losses in humans has not been quantified. If microbial synthesis is substantial, balance studies in humans may have underestimated pantothenic acid absorption and requirements.
Coenzyme A (CoA) is hydrolyzed to pantothenate in a multiple-step reaction. The pantothenic acid is excreted intact in urine, ... . The amount excreted varies proportionally with dietary intake over a discrete yet wide range of intake values.

Interactions
Although the clinical importance has not been established, the miotic effects of anticholinesterase ophthalmic preparations (eg, echothiophate iodide (no longer commercially available in the US), isoflurophate) reportedly may be potentiated by pantothenic acid.
The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity ... induced by single injection of aurothioglucose (300 mg/kg body wt, ip). All the tested substances were administered during the last 10 days before decapitation (im, of dosage equivalent to 150 mg/kg body wt of phosphopantothenate). The studied substances inhibited the weight gain of the animals with hypothalamic obesity over the last 10 days of the experiment. The treatment with aurothioglucose increased food intake and mean body weight, blood glucose level; insulin, serum total cholesterol, triglyceride, the sum of LDL + VLDL and LDL-cholesterol concentration; triglyceride and cholesterol fractions in the liver; triglyceride and FFA content as well as lipoprotein lipase activity in adipose tissue of experimental mice. The administration of the assay compounds lowered food intake and mean body weight, insulin and glucose levels and decreased the content of triglycerides, total cholesterol and cholesterol esters in serum and adipose tissue as well as raised the activity of lipoprotein lipase in adipose tissue and serum lipolytic activity in obese mice. Among the compounds studied the reverse effect of panthenol was especially pronounced. The mechanism of hypolipidemic effects of pantothenic acid derivatives can be related to the reduced resistance to insulin and activation of lipolysis in serum and adipose tissue. /Panthenol, Phosphopantothenate, Pantethine/
A combination of 1.2 g of calcium pantothenate, 0.6 g of pyridoxine, 3 g of niacinamide, and 3 g of ascorbic acid taken daily for 6 weeks was associated with elevations in serum transaminase levels in children. One of these doses or the combination may therefore cause hepatotoxicity, but it is not possible from this study alone to ascribe to pantothenic acid the reported adverse effect in liver function.
... Pregnant CD-1 mice were administered a teratogenic dose of valproic acid (VPA) prior to neural tube closure and embryonic protein levels were analyzed. ... VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with a neural tube defect (NTD) showed a 2-fold increase in p53, and 4-fold decreases in NF-kappaB, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P<0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P<0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P<0.05). Folic acid also reduced VPA-induced alterations in p53, NF-kappaB, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-kappaB, Pim-1, and c-Myb...
For more Interactions (Complete) data for D-Pantothenic Acid (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat sc 3500 mg/kg
LD50 Mouse ip 1443 mg/kg
LD50 Mouse sc 2500 mg/kg

[1]. Shuai Chen, et al. Metabolomic analysis of the toxic effect of chronic exposure of cadmium on rat urine. Environ Sci Pollut Res Int. 2018 Feb;25(4):3765-3774.
[2]. M Sato, et al. Pantothenic acid decreases valproic acid-induced neural tube defects in mice (I). Teratology. 1995 Sep;52(3):143-8.

Therapeutic Uses
A butyryl-beta-alanine that can also be viewed as pantoic acid complexed with BETA ALANINE. It is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE.
Pantothenic acid is not generally accepted as having any therapeutic use, but it has been prescribed for streptomycin neurotoxicity, salicylate toxicity, gray hair, alopecia, catarrhal respiratory disorders, osteoarthritis, diabetic neuropathy, psychiatric states, and to ameliorate untoward symptoms during thyroid therapy in patients with congenital hypothyroidism (cretinism).
Pantothenic acid has been used for a wide range of disorders such as acne, alopecia, allergies, burning feet, asthma, grey hair, dandruff, cholesterol lowering, improving exercise performance, depression, osteoarthritis, rheumatoid arthritis, multiple sclerosis, stress, shingles, ageing and Parkinson's disease. It has been investigated in clinical trials for arthritis, cholesterol lowering and exercise performance.[Mason P; Dietary Supplements,
Pantothenic acid deficiency has rarely been identified in humans except in conjunction with deficiency of other B complex vitamins. Diagnosis of pantothenic acid deficiency is aided by a serum pantothenate concentration of less than 50 mcg/mL. Whenever possible, poor dietary habits should be corrected, and some clinicians recommend administration of multivitamin preparations containing pantothenic acid in patients with vitamin deficiencies since poor dietary habits may result in concurrent deficiencies.
For more Therapeutic Uses (Complete) data for D-Pantothenic Acid (10 total), please visit the HSDB record page.

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Drug Warnings
...This vitamin should not be used alone ... /and/ since no data are available on the effects of topical preparations, these should not be used.
A 76-year-old white woman was admitted to the hospital because of chest pain and dyspnea related to pleurisy and a pericardial tamponade. This patient had no history of allergy and had been taking vitamins B5 and H for two months. ... After withdrawal of the vitamins, the patient recovered and the eosinophilia disappeared. ... This case suggests that vitamins B5 and H may cause symptomatic, life-threatening, eosinophilic pleuropericarditis. Physicians prescribing these commonly used vitamins should be aware of this potential adverse reaction.
A report of life-threatening eosinophilic pleuropericarditis associated with the use of biotin and panthothenic acid. Symptoms resolved on stopping the vitamins.
... Three patients (two are brothers) with confirmed Barth syndrome /were/ treated with pantothenic acid. This treatment is still controversial and only one study has reported positive results to date. In /the three/ patients, long-term treatment has failed to reduce the number of infectious episodes and prevent dilated cardiomyopathy...

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Pharmacodynamics
Pantothenic acid is used in the synthesis of coenzyme A (CoA). CoA is thought to act as a carrier molecule, allowing the entry of acyl groups into cells. This is of critical importance as these acyl groups are used as substrates in the tricarboxylic acid cycle to generate energy and in the synthesis of fatty acids, cholesterol, and acetylcholine. Additionally, CoA is part of acyl carrier protein (ACP), which is required in the synthesis of fatty acids in addition to CoAs use as a substrate. Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively. Since pantothenic acid participates in a wide array of key biological roles, it may have numerous wide-ranging effects.

C₉H₁₇NO₅

219.24

219.11

79-83-4

6613

Yellow viscous oil
Viscous oil
Viscous hygroscopic liquid

1.266

490.2±55.0 °C at 760 mmHg

178-179ºC

250.3±31.5 °C

0.0±2.8 mmHg at 25°C

1.510

-0.35

4

5

6

15

239

1

[C@H](O)(C(=O)NCCC(=O)O)C(C)(C)CO

GHOKWGTUZJEAQD-ZETCQYMHSA-N

InChI=1S/C9H17NO5/c1-9(2,5-11)7(14)8(15)10-4-3-6(12)13/h7,11,14H,3-5H2,1-2H3,(H,10,15)(H,12,13)/t7-/m0/s1

3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoic acid

vitamin B5; pantothenate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~50 mg/mL (~228.07 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (11.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (11.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (456.14 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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