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 exists primarily as coenzyme A (CoA) or acid phosphatase (ACP), and must be converted to free pantothenic acid for absorption. CoA and ACP are hydrolyzed to 4'-phosphopantoylthioethylamine, which is then dephosphorylated to pantothenicylthioethylamine, subsequently hydrolyzed again in the intestinal lumen by pantothenicylthioethylaminease to free pantothenic acid. Free pantothenic acid is absorbed by intestinal cells via a saturable, sodium-dependent active transport system, with passive diffusion as an auxiliary pathway. When intake increases tenfold, absorption may drop below 10% due to transporter saturation. Pantothenic acid is absorbed via active transport at low concentrations in the small intestine and via passive transport at high concentrations. Because the active transport system is saturable, absorption efficiency is lower at high concentrations. However, the exact intake level at which absorption decreases is currently unknown. The amount of pantothenic acid excreted in urine is proportional to dietary intake over a wide range of intake levels. Pantothenic acid is readily absorbed from the gastrointestinal tract. It is present in all tissues, with concentrations ranging from 2 to 45 micrograms per gram. Since intake and excretion are roughly equal, pantothenic acid appears to be largely undigested in the body. Approximately 70% of unmetabolized pantothenic acid is excreted in urine and approximately 30% in feces. After oral administration, pantothenic acid is readily absorbed from the gastrointestinal tract. Normal serum pantothenic acid concentration is 100 micrograms per milliliter or higher. Pantothenic acid is widely distributed throughout the body, primarily in the form of coenzyme A. The highest concentrations are found in the liver, adrenal glands, heart, and kidneys. The breast milk of a lactating mother with a normal diet contains approximately 2 micrograms of pantothenic acid per milliliter. After oral administration, approximately 70% of pantothenic acid is excreted unchanged in urine and approximately 30% in feces. Newborns have significantly higher pantothenic acid levels than their mothers. At full term, the mean pantothenic acid level in 174 mothers was 430 ng/mL (range 250–710 ng/mL), and the mean pantothenic acid level in newborns was 780 ng/mL (range 400–1480 ng/mL). Pantothenic acid is transferred to the fetus via active placental transport, but at a slower rate than other B vitamins. One report showed that pantothenic acid levels in low birth weight infants were significantly lower than in normal birth weight infants. For more complete data on the absorption, distribution, and excretion of D-pantothenic acid (20 items), please visit the HSDB record page.
Metabolism/Metabolites
The synthesis of coenzyme A (CoA) from pantothenic acid is primarily regulated by pantothenic acid kinase, which is inhibited by the pathway end product CoA and acyl-CoA. D-pantothenic acid is essential for the intermediate metabolism of carbohydrates, proteins, and lipids. Pantothenic acid is a precursor to coenzyme A, which is essential for acetylation (acyl activation) in gluconeogenesis. Coenzyme A participates 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.
CoA (CoA) absorption: Dietary CoA is hydrolyzed in the intestinal lumen to dephosphated CoA, phosphate pantothenic acid thioethylamine, and pantothenic acid thioethylamine, which is subsequently hydrolyzed to pantothenic acid. In studies of the absorption of various forms of pantothenic acid, pantothenic acid is the only pantothenic acid-containing compound that can be absorbed by rats. In animal models, low concentrations of vitamin A are absorbed via active transport, while high concentrations are absorbed via passive transport. Due to the saturation of the active transport system, the higher the intake concentration, the lower the absorption efficiency; however, the intake level at which absorption efficiency decreases in humans is unclear.
Pantothenic acid has been observed to be synthesized by the gut microbiota in mice, but the contribution of bacterial synthesis to pantothenic acid levels in humans or to fecal excretion has not been quantified. If the amount synthesized by microorganisms is large, human balance studies may underestimate the absorption and requirement of pantothenic acid. Coenzyme A (CoA) is hydrolyzed into pantothenic acid through a multi-step reaction. Pantothenic acid is excreted intact in urine… Within a certain but relatively wide range of intake, its excretion is directly proportional to dietary intake.

Interactions
While the clinical significance remains undetermined, it has been reported that the miotic effects of anticholinesterase ophthalmic preparations (e.g., etorizine iodide (discontinued in the US), isoflurane) may be enhanced by pantothenic acid. This study investigated the lipid-lowering effects of pantothenic acid derivatives (pantothenic acid phosphate, panthenol, and pantothenic acid thioethylamine) in hypothalamic obese mice… Hypothalamic obesity was induced by a single intraperitoneal injection of glucosinolate (300 mg/kg body weight). All test substances were administered 10 days prior to decapitation (intramuscular injection, equivalent to 150 mg/kg body weight of pantothenic acid phosphate). The test substances inhibited weight gain in hypothalamic obese mice during the last 10 days of the experiment. Treatment with glucosinolates increased food intake, average body weight, and blood glucose levels. This study examined insulin, serum total cholesterol, triglycerides, the sum of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), and LDL cholesterol concentration in experimental mice; triglyceride and cholesterol components in the liver; triglyceride and free fatty acid (FFA) content in adipose tissue; and lipoprotein lipase activity. The results showed that administration of the tested compounds reduced food intake and average body weight, insulin and glucose levels in obese mice, and decreased serum and adipose tissue triglyceride, total cholesterol, and cholesterol ester content, while increasing lipoprotein lipase activity in adipose tissue and serum lipolysis activity. Among the compounds studied, panthenol showed the most significant reversal effect. The lipid-lowering mechanism of pantothenic acid derivatives may be related to reducing insulin resistance and activating lipolysis in serum and adipose tissue. Panthenol, pantothenic acid phosphate, and pantothenic acid/
daily administration of 1.2 g calcium pantothenate, 0.6 g pyridoxine, 3 g nicotinamide, and 3 g ascorbic acid for 6 weeks was associated with elevated serum transaminase levels in children. Therefore, any one or a combination of these doses could potentially cause hepatotoxicity, but this study alone cannot attribute the reported adverse liver function to pantothenic acid.
…Pregnant CD1 mice were injected with teratogenic doses of valproic acid (VPA) before neural tube closure, and embryonic protein levels were analyzed. Valproic acid (VPA, 400 mg/kg)-induced neural tube defects (NTDs, incidence 24%) and embryos exposed to VPA with neural tube defects showed a 2-fold increase in p53 protein levels and a 4-fold decrease in NF-κB, Pim-1, and c-Myb protein levels compared to phenotypically normal littermates (P<0.05). Furthermore, VPA also increased the embryonic Bax/Bcl-2 protein level ratio (P<0.05). Pretreatment of pregnant mice with folic acid or pantothenic acid before administration of VPA significantly reduced the incidence of VPA-induced neural tube defects (P<0.05). Folic acid also reduced VPA-induced changes in p53, NF-κB, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced changes in NF-κB, Pim-1, and c-Myb protein levels…
For more complete data on D-pantothenic acid interactions (6 in total), please visit the HSDB record page.

---

Non-human toxicity values
Rat subcutaneous LD50: 3500 mg/kg
Mouse intraperitoneal LD50: 1443 mg/kg
Mouse subcutaneous LD50: 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
Butyryl-β-alanine, also known as pantothenic acid, is a complex of pantothenic acid and β-alanine. It is integrated into coenzyme A and protects cells from oxidative damage by increasing glutathione levels. Pantothenic acid is not generally considered to have any therapeutic uses, but it has been used to treat streptomycin neurotoxicity, salicylate toxicity, gray hair, hair loss, catarrhal respiratory diseases, osteoarthritis, diabetic neuropathy, mental illness, and to alleviate adverse symptoms during thyroid treatment in patients with congenital hypothyroidism (cretinism). Pantothenic acid has been used to treat a variety of conditions, including acne, hair loss, allergies, plantar fasciitis, asthma, gray hair, dandruff, lowering cholesterol, improving athletic performance, depression, osteoarthritis, rheumatoid arthritis, multiple sclerosis, stress, shingles, aging, and Parkinson's disease. It has been studied in clinical trials for arthritis, lowering cholesterol, and improving athletic performance. [Mason P; Dietary Supplements] Pantothenic acid deficiency is rare in humans and usually occurs concurrently with other B vitamin deficiencies. A serum pantothenic acid concentration below 50 mcg/mL is helpful in diagnosing pantothenic acid deficiency. Poor dietary habits should be corrected as much as possible. Some clinicians recommend that patients with vitamin deficiencies take multivitamin preparations containing pantothenic acid, as poor dietary habits can lead to simultaneous deficiencies in multiple vitamins. For more complete data on the therapeutic uses of D-pantothenic acid (10 in total), please visit the HSDB record page.

---

Drug Warning
…This vitamin should not be used alone…/and/due to a lack of data on the effects of topical preparations, topical preparations should not be used. A 76-year-old white woman was admitted to the hospital with chest pain and dyspnea due to pleurisy and cardiac tamponade. The patient had no history of allergies and had been taking vitamin B5 and H for two months. …After discontinuing the vitamins, the patient recovered, and the eosinophilia disappeared. …This case suggests that vitamin B5 and H may cause symptomatic, life-threatening eosinophilic pleurocarditis. Physicians should be aware of this potential adverse reaction when prescribing these commonly used vitamins.
A report of a life-threatening case of eosinophilic pleurocarditis associated with biotin and pantothenic acid use. Symptoms improved after discontinuation of the vitamin.
…Three patients diagnosed with Bart syndrome (two of whom were brothers) received pantothenic acid treatment. This treatment remains controversial, with only one study reporting positive results to date. In these three patients, long-term treatment failed to reduce the frequency of infections or prevent dilated cardiomyopathy…

---

Pharmacodynamics
Pantothenic acid is involved in the synthesis of coenzyme A (CoA). CoA is considered a carrier molecule that allows acyl groups to enter cells. This is crucial because these acyl groups are substrates of the tricarboxylic acid cycle, used to produce energy and synthesize fatty acids, cholesterol, and acetylcholine. Furthermore, CoA is a component of acyl carrier proteins (ACPs), which, in addition to serving as substrates for CoA, are involved in fatty acid synthesis. Pantothenic acid in the CoA form is also essential for acylation and acetylation, for example, in signal transduction and enzyme activation and inactivation, respectively. Because pantothenic acid is involved in many key biological processes, it may have a wide range of impacts.

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.

---

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.

---

View More

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.

---

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.

---

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