Absorption, Distribution and Excretion
Following oral administration, nystatin is minimally absorbed systemically, and detectable plasma concentrations are not achieved after topical or vaginal administration. Most orally administered nystatin is excreted unchanged in feces. Nystatin is not absorbed into the systemic circulation and therefore does not distribute. Nystatin is poorly penetrating the eyes. Absorption of nystatin in the gastrointestinal tract is also poor, and detectable plasma concentrations are not achieved after commonly used doses. After oral administration, almost all nystatin is excreted unchanged in feces. In healthy individuals, after concurrent oral administration of two nystatin tablets (400,000 units), the average concentration of nystatin in saliva remained above the concentration required for in vitro inhibition of clinically important Candida albicans for approximately 2 hours after initial dissolution. Topical application to intact skin or mucous membranes does not result in absorption. For more complete data on the absorption, distribution, and excretion of nystatins (6 in total), please visit the HSDB records page.

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Metabolism / Metabolites
Because nystatin is hardly absorbed throughout the body, it is not metabolized to any significant extent.

Toxicity Summary
Nystatin interacts with 14α-demethylase, a cytochrome P-450 enzyme essential for the conversion of lanosterol to ergosterol. This leads to inhibition of ergosterol synthesis and increased fungal cell membrane permeability. Nystatin exerts its antifungal activity by binding to ergosterol on the fungal cell membrane. This binding creates pores in the cell membrane. Potassium and other cellular components leak from these pores, leading to cell death.

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Hepatotoxicity
Nystatin treatment is associated with a lower incidence of serum enzyme abnormalities, although it is difficult to attribute these elevations to nystatin. Despite nystatin's decades of use, there is no conclusive evidence linking it to acute liver injury. Although nystatin is not normally absorbed, low concentrations may enter the bloodstream in patients with gastrointestinal inflammation and injury. Nevertheless, nystatin is considered very safe and unlikely to cause liver injury. Probability score: E (unlikely to cause clinically apparent liver injury).

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Protein Binding
Nystatin is not absorbed into the systemic circulation and is therefore unaffected by plasma protein binding.

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Non-Human Toxicity Values
Intraperitoneal LD50 in mice: 200 mg/kg

[1]. Michel, et al. "Nystatin." Analytical profiles of drug substances. Vol. 6. Academic Press, 1977. 341-421.

Nystatin A1 is a polyene macrolide antibiotic and a component of nystatin complexes produced by various Streptomyces. It is an antifungal antibiotic used to treat localized fungal infections caused by a variety of fungal pathogens, including yeast-like and filamentous fungi. Nystatin is a polyene antifungal drug with broad-spectrum bactericidal and bacteriostatic activity against a wide range of yeasts and fungi, particularly Candida. It is one of the most potent antifungal agents synthesized by bacteria (in this case, Streptomyces norovirus), closely related to amphotericin B, with only slight structural differences. Nystatin has stronger antifungal activity than amphotericin B, but parenteral nystatin is significantly toxic, and there are currently no formulations suitable for systemic administration. Due to minimal absorption after oral or topical administration, the efficacy of nystatin is limited to the treatment/prevention of fungal infections of the skin, mucosae, and gastrointestinal tract. Nystatin is a polyene antifungal drug. Nystatin is a topical and oral antifungal drug effective against various yeasts and Candida albicans, primarily used to treat cutaneous and oropharyngeal candidiasis. Nystatin is not absorbed orally, and there are no reports of drug-induced liver injury. Nystatin A1 has been reported to be present in *Streptomyces aquaponica*, *Candida glaucum*, and other microorganisms with relevant data. Nystatin is a polyene macrolide antibiotic with antifungal activity. After administration, nystatin binds to sterols in the fungal plasma membrane, thereby increasing membrane permeability. This leads to leakage of important intracellular components, cell rupture, and ultimately fungal cell death. Nystatin is a polyene antifungal drug to which many molds and yeasts (including *Candida*) are sensitive. Intravenous nystatin has some toxicity, but it is not absorbed through intact skin or mucous membranes. It is considered a relatively safe drug for treating oral or gastrointestinal fungal infections. See also: Nystatin A3 (related); Nystatin; Triamcinolone (note moved); Iodoquinol; Nystatin (note moved)... See more...

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Drug Indication
Nystatin is available in oral formulations for the treatment and/or prevention of oral candidiasis (also known as thrush), intestinal candidiasis, and anal candidiasis. It can also be used topically to treat vulvovaginal candidiasis and other cutaneous candidiasis. A combination formulation (Viaderm KC®) containing nystatin, neomycin, bacitracin D, and triamcinolone acetonide is indicated for the treatment of corticosteroid-sensitive skin conditions caused by bacterial or Candida infections, as well as anal/vulvar pruritus. It can also be used in combination with metronidazole to treat mixed infections caused by Trichomonas vaginalis and Candida albicans. Nystatin is sometimes used to prevent invasive candidiasis in low birth weight newborns, but is usually used as a second-line treatment after fluconazole. FDA label.

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Mechanism of Action
Nystatin A1 is a channel-forming ionocarrier, meaning it exerts its therapeutic effect by forming transmembrane pores on the fungal plasma membrane. The formation of these pores leads to altered membrane permeability, causing leakage of intracellular substances and disrupting the electrochemical gradients required for normal cellular function. Nystatin exhibits higher selectivity for fungal cells than mammalian cells because its binding affinity for ergosterol, a key sterol in the fungal cell wall, is higher than that for its mammalian counterpart, cholesterol. Nystatin exerts its antifungal activity by binding to sterols in the fungal cell membrane. This drug is ineffective against microorganisms (such as bacteria) whose cell membranes do not contain sterols. Due to this binding, the cell membrane can no longer function as a selective barrier, leading to the loss of potassium ions and other cellular components. …Antimicrobial agents that act directly on the microbial cell membrane, affecting cell membrane permeability and causing leakage of intracellular compounds; these antimicrobial agents include…the polyene antifungal agent nystatin…which binds to cell wall sterols…

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Therapeutic Uses
Antibiotics, antifungal drugs; antibiotics, macrolides; ionocarriers
Veterinary drugs: antifungal drugs; growth promoters
Veterinary drugs: /for the treatment/of intestinal fungal infections caused by Candida albicans in poultry; occasionally for cats and dogs in cases of suspected Candida intestinal overgrowth after antibiotic treatment, or for topical application...in cream or ointment form for skin lesions...
Nystatin vaginal tablets can be used as lozenges to treat oropharyngeal candidiasis because their slow dissolution prolongs the contact time between the drug and the oral cavity. /Not included in the US product label/
For more complete data on the therapeutic uses of nystatin (9 types), please visit the HSDB record page.

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Drug Warnings
Whether Nystatin A1 is excreted into human breast milk should be investigated, and breastfeeding women should use this medication with caution. The incidence of adverse reactions to oral nystatin treatment is low. Mild and transient nausea, vomiting, gastrointestinal discomfort, and diarrhea have been reported; these gastrointestinal adverse reactions are most likely to occur with high oral doses (e.g., more than 5 million units daily). Hypersensitivity reactions have been reported in very rare cases. Patients should be advised to contact their doctor immediately if irritation or allergic symptoms occur during nystatin treatment. Patients should be warned that vaginal nystatin treatment should not be interrupted or stopped during the prescribed course of treatment, even during menstruation or after symptoms have subsided a few days after treatment, unless otherwise instructed by their doctor. Patients should be informed that adjunctive measures (such as therapeutic vaginal douching) are not necessary or even recommended during vaginal nystatin treatment. However, non-pregnant women may use vaginal douches if they wish to improve their appearance. Adverse reactions to topical nystatin are extremely rare even with long-term use. Irritation is rare. Allergic reactions to nystatin are extremely rare; however, preservatives in certain formulations (such as ethylenediamine, parabens, and thimerosal) are associated with a higher incidence of contact dermatitis. In rare cases, acne-like rashes may occur after topical application of nystatin and triamcinolone. For more complete data on nystatin (9 in total), please visit the HSDB record page.

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Pharmacodynamics
Nystatin A1 is an antifungal drug that, in vitro, has been shown to have antifungal and bactericidal effects against various yeasts and yeast-like fungi. Its antifungal mechanism involves disrupting the fungal cell membrane. *Candida albicans* exhibits very low resistance to nystatin, but other *Candida* species readily develop resistance. Nystatin has virtually no activity against bacteria, protozoa, or viruses. It has significant systemic toxicity, and currently there are no formulations suitable for systemic administration—therefore, its efficacy is currently limited to local, oral, and gastrointestinal infections.

C47H75NO17

926.09

925.503

34786-70-4

11286230

Light yellow powder Yellow to tan powder

1.33g/cm3

1132.2ºC at 760mmHg

Gradually decomp above 160 °C without melting by 250 °C

638.5ºC

1.606

1.443

12

18

3

65

1620

19

C[C@H]1C=CC=CCCC=CC=CC=CC=C[C@@H](C[C@H]2[C@@H]([C@H](C[C@](C[C@H]([C@@H](CC[C@H](C[C@H](C[C@H](CC(=O)O[C@@H](C)[C@H](C)[C@@H]1O)O)O)O)O)O)(O)O2)O)C(=O)O)O[C@H]3[C@H]([C@H]([C@@H]([C@@H](C)O3)O)N)O

VQOXZBDYSJBXMA-NQTDYLQESA-N

InChI=1S/C47H75NO17/c1-27-17-15-13-11-9-7-5-6-8-10-12-14-16-18-34(64-46-44(58)41(48)43(57)30(4)63-46)24-38-40(45(59)60)37(54)26-47(61,65-38)25-36(53)35(52)20-19-31(49)21-32(50)22-33(51)23-39(55)62-29(3)28(2)42(27)56/h5-6,8,10-18,27-38,40-44,46,49-54,56-58,61H,7,9,19-26,48H2,1-4H3,(H,59,60)/b6-5+,10-8+,13-11+,14-12+,17-15+,18-16+/t27-,28-,29-,30+,31+,32+,33+,34-,35+,36+,37-,38-,40+,41-,42+,43+,44-,46-,47+/m0/s1

(1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid

Nystatin A1

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)