Anti-fungal

All six species of Candida have significantly less buccal epithelial cell adhesion when using nystatin[1].
The antibiotic nystatin makes plasma membranes more permeable to chloridion and other small monovalent ions. Nystatin increases apical permeability of chloridion to the extent that transport across the basolateral membrane of tracheal epithelial cells limits transepithelial chloridion transport, mainly due to cotransporter activity. Nystatin (400 units/mL) abolishes UTP stimulation of transepithelial 36Cl flux and raises its basal level by about 1.5 times. Nystatin treatment also abolishes UTP stimulation of saturable, basolateral [3H]bumetanide binding, a measure of functioning Na-K-Cl cotransporters in these cells; isoproterenol stimulation of binding is only mildly inhibited by nystatin treatment[2].
By primarily promoting the clathrin-mediated pathway for endostatin internalization, nystatin dramatically increases the uptake of endostatin by endothelial cells. Nystatin-induced increased absorption of? Additionally, endostatin intensifies its inhibitory actions on the migration and formation of endothelial cell tubes[3].

Endostatin's antiangiogenic and antitumor efficacies in vivo are eventually increased when nystatin and endostatin are combined because they specifically increase endostatin uptake and biodistribution in tumor blood vessels and tumor tissues but not in the normal tissues of tumor-bearing mice[3].When compared to the no-treatment, saline, or empty-liposome groups, liposomal Nystatin, at doses as low as 2 mg/kg of body weight/day, protects neutropenic mice against Aspergillus-induced death in a statistically significant way at the 50-day time point[4].

Absorption, Distribution and Excretion
Nystatin is minimally absorbed systemically after oral administration, 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. Nystatin is poorly absorbed in the gastrointestinal tract, and detectable plasma concentrations are not achieved after commonly used doses. After oral administration, nystatin is almost entirely excreted unchanged in feces. In healthy individuals, after simultaneous oral administration of two nystatin tablets (400,000 units), the average concentration of nystatin in saliva remained higher than the concentration required in vitro to inhibit the growth of clinically important Candida species for approximately 2 hours after initial dissolution. It is not absorbed when applied topically to intact skin or mucous membranes. For more complete data on the absorption, distribution, and excretion of nystatin (6 items in total), please visit the HSDB record page. Metabolites/Metabolites: Because nystatin is hardly absorbed systemically, its metabolism is very low.

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. While nystatin is generally not 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). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation While there is currently no information on nystatin excretion in breast milk, its oral absorption rate is extremely low, therefore most reviewers and clinicians consider it safe for breastfeeding women to use nystatin, including topical application to the nipples. Only water-soluble creams or gels should be applied to the breasts, as ointments may expose the infant to high concentrations of mineral oil through licking. Excess cream should be removed from the nipples before breastfeeding. Nystatin is less effective than other topical medications in treating oral thrush.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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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]. Adhesion of oral Candida species to human buccal epithelial cells following brief exposure to nystatin. Oral Microbiol Immunol. 1999 Dec;14(6):358-63.

[2]. Na-K-Cl cotransport in nystatin-treated tracheal cells: regulation by isoproterenol, apical UTP, and [Cl]i. Am J Physiol. 1994 May;266(5 Pt 1):C1440-52.

[3]. Cholesterol sequestration by nystatin enhances the uptake and activity of endostatin in endothelium via regulating distinct endocytic pathways. Blood. 2011 Jun 9;117(23):6392-403.

[4]. Activity of liposomal nystatin against disseminated Aspergillus fumigatus infection in neutropenic mice. Antimicrob Agents Chemother. 1997 Oct;41(10):2238-43.

[5]. Oxaliplatin enhances TRAIL-induced apoptosis in gastric cancer cells by CBL-regulated death receptor redistribution in lipid rafts.FEBS Lett. 2009 Mar 4;583(5):943-8.

Therapeutic Uses

Antibiotics, antifungal drugs; antibiotics, macrolides; ionocarriers

Veterinary drugs: antifungal drugs; growth promoters

Veterinary drugs: used to treat intestinal fungal infections caused by Candida albicans in poultry; occasionally used to treat suspected Candida intestinal overgrowth in cats and dogs after antibiotic treatment. It can be taken orally or applied topically… as a cream or ointment to 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.
Drug Warnings

Because it is unclear whether nystatin is excreted into human milk, breastfeeding women should use this drug 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 if irritation or allergic symptoms occur during nystatin treatment. Patients should be told 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 (e.g., therapeutic vaginal douching) are not necessary or even recommended during vaginal nystatin treatment; however, non-pregnant women may use cleansing vaginal douches for cosmetic purposes. Adverse reactions to topical nystatin are very rare, even with prolonged use. Irritation is rare. Hypersensitivity reactions to nystatin are also rarely reported; however, preservatives in certain formulations (e.g., ethylenediamine, parabens, 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 drug warnings for nystatin (9 in total), please visit the HSDB record page. Pharmacodynamics: Nystatin is an antifungal drug that has been shown to have antifungal and bactericidal effects against a variety of yeasts and yeast-like fungi in vitro. It exerts its antifungal effect by disrupting the fungal cell membrane. Candida albicans exhibits very low resistance to nystatin, but other Candida species readily develop resistance. Nystatin has no significant activity against bacteria, protozoa, or viruses. It has significant systemic toxicity, and there are currently no formulations suitable for systemic administration—therefore, its efficacy is currently limited to topical, oral, and gastrointestinal infections.

C47H75NO17

926.110

276.208

C, 60.96; H, 8.16; N, 1.51; O, 29.37

1400-61-9

11286230

Light yellow to khaki solid powder

0.9±0.1 g/cm3

400.2±14.0 °C at 760 mmHg

>155°C (dec.)

297.0±15.2 °C

0.0±2.0 mmHg at 25°C

1.504

6.14

12

18

3

65

1620

19

O1C2([H])C([H])([H])C([H])(C([H])=C([H])C([H])=C([H])C([H])=C([H])C([H])=C([H])C([H])([H])C([H])([H])C([H])=C([H])C([H])=C([H])[C@@]([H])(C([H])([H])[H])[C@@]([H])([C@]([H])(C([H])([H])[H])[C@@]([H])(C([H])([H])[H])OC(C([H])([H])C([H])(C([H])([H])C([H])(C([H])([H])C([H])(C([H])([H])C([H])([H])C([H])(C([H])(C([H])([H])[C@]1(C([H])([H])C([H])(C2([H])C(=O)O[H])O[H])O[H])O[H])O[H])O[H])O[H])O[H])=O)O[H])O[C@@]1([H])[C@@]([H])([C@@]([H])([C@]([H])([C@]([H])(C([H])([H])[H])O1)O[H])N([H])[H])O[H] |c:9,13,17,21,31,35|

VQOXZBDYSJBXMA-JKMCSYCMSA-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,3S,4R,7R,9R,11S,15S,16R,17R,18S,19E,21E,25Z,27E,29E,31E,33S,35S,36S,37S)-33-(((2S,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyltetrahydro-2H-pyran-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; Mycostatin. AI3-26526; Barstatin 100; Biofanal; Candex; Candex Lotion; Candio-hermal; Diastatin; Fungicidin; Herniocid; HSDB 3138; Korostatin; Moronal; Myconystatin; Mycostatin; Nilstat; Nistatin; Nistatina; NSC 150817; Nyamyc; Nyotran; Nysert; Nystan; Nystatin; Nystatine; Nystavescent; Nystex; Nystop; O-V Statin; Stamycin; Zydin E

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.

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 (~53.99 mM)

Solubility in Formulation 1: 2.5 mg/mL (2.70 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), suspension solution; with sonication.
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 (2.70 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 (2.70 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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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 (Please use freshly prepared in vivo formulations for optimal results.)