Macrolide antibiotic

Plasmodium falciparum cannot develop in the presence of erythromycin stearate, which has IC50 and IC90 values of 58.2 μM and 104.0 μM, respectively [1]. In addition to its anti-inflammatory and antioxidant properties, erythromycin stearate (10 μM, 100 μM; 24 hours, 72 hours) also dramatically lowers the expression of TNF-α (p<0.01) and Iba-1 (p<0.01) and prevents the formation of 4-HNE (p<0.01) and 8-OHdG (p<0.01) [4].

Erythromycin stearate (gastric intubation; 0.1-50 mg/kg; 30-120 days) decreases tumor growth and prolongs survival in mice at a dose of 5 mg/kg [3]. Erythromycin stearate (gastric intubation; 5 mg/kg) maintained mouse survival even at 120 days postinoculation, whereas a dose of 50 mg/kg decreased the mean survival period of tumor-bearing mice by 4- 5 days[3]. Erythromycin stearate (ih; single injection; 50 mg/kg) has a protective effect on brain ischemia-reperfusion injury rat model [4].

Cell viability assay [4]
Cell Types: Embryonic primary cortical neurons (from the cerebral cortex of 17-day-old Sprague-Dawley rats)
Tested Concentrations: 10, 100 μM
Incubation Duration: 24, 72 hrs (hours)
Experimental Results: Improved viability of cultured neurons 3 hrs (hours) of oxygen-glucose deprivation (OGD) in vitro cells.

Animal/Disease Models: Female ddY mice (6 weeks old) with EAC cells or CDF mice (6 weeks old) with P388 cells [3]
Doses: 0.1 mg/kg; 0.5 mg/kg; 10 mg/kg ; 30 mg/kg; 50 mg/kg
Route of Administration: gastric intubation; 30-120 days
Experimental Results: After the 5 mg/kg dose, tumor growth was diminished and the average survival time of mice was prolonged, but the 50 mg/kg dose shortened the load. MST of tumor mice.

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Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (8 weeks old, 250-300 g) [4]
Doses: 50 mg/kg
Route of Administration: Single subcutaneous injection
Experimental Results: Reduce infarct volume and edema volume, and improve neurological deficits.

Absorption, Distribution and Excretion
Four hours after oral administration of 250 mg of erythromycin, the peak plasma concentration is 0.3–0.5 μg/mL; after oral administration of 500 mg tablets, the peak plasma concentration is 0.3–1.9 μg/mL. Various erythromycin esters have been prepared to improve stability and promote absorption. After oral administration of stearates, the plasma concentration of erythromycin does not change significantly. Erythromycin readily diffuses into intracellular fluid and exhibits antibacterial activity in all sites except the brain and cerebrospinal fluid. …One of the few antibiotics that can penetrate prostatic fluid, reaching approximately 40% of plasma concentration. The degree of binding to plasma proteins varies…the binding rate may exceed 70% in all dosage forms. Erythromycin Erythromycin alkaloids are readily absorbed in the upper small intestine; it is inactivated by gastric juices…food in the stomach delays its final absorption. Erythromycin Erythromycin can cross the placental barrier; the drug concentration in fetal plasma is approximately 5–20% of the concentration in maternal circulation. /Erythromycin/
For more complete data on the absorption, distribution, and excretion of erythromycin stearate (11 metabolites), please visit the HSDB record page.

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Metabolism/Metabolites
It is hydrolyzed in the small intestine and tissues to form erythromycin.

Medication Use During Pregnancy and Lactation ◉ Overview of Medication Use During Lactation
Since erythromycin is present in low concentrations in breast milk and can be safely administered directly to infants, it is safe for breastfeeding women to use. The small amount of erythromycin in breast milk is unlikely to have adverse effects on the infant. Close monitoring of the infant's irritability and potential effects on the gut microbiota, such as diarrhea, candidiasis (thrush, diaper rash), is necessary. One case report and unconfirmed epidemiological evidence suggest that erythromycin use by the mother during the first two weeks of breastfeeding may lead to hypertrophic pyloric stenosis in the infant; however, even if it occurs, the frequency is extremely low, and this association has been questioned.
Topical application for acne treatment is unlikely to cause side effects in the infant, but topical application to the nipples may increase the risk of diarrhea in the infant. 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. [1]
◉ Effects on breastfed infants
A 3-week-old infant was reported to have pyloric stenosis, vomiting, sedation, poor sucking, and slow weight gain, symptoms that may be related to erythromycin in breast milk. [4]
A cohort study of infants diagnosed with hypertrophic pyloric stenosis found that mothers of affected infants were 2.3 to 3 times more likely to have taken macrolide antibiotics within 90 days postpartum than other infants. Stratified analysis of the infants showed an odds ratio of 10 for female infants and 2 for male infants. All affected infants were breastfed. 72% of macrolide prescriptions were erythromycin. However, the authors did not specify which macrolide antibiotics the affected infants' mothers took. [5] A study comparing infants breastfed by mothers taking amoxicillin with infants breastfed by mothers taking macrolide antibiotics found no cases of pyloric stenosis in either group. However, most infants exposed to macrolide antibiotics through breast milk were exposed to roxithromycin. Of the 55 infants exposed to macrolide antibiotics, only 2 had been exposed to erythromycin. 12.7% of the infants exposed to macrolide antibiotics experienced adverse reactions, a rate similar to that of infants exposed to amoxicillin. Adverse reactions included rash, diarrhea, loss of appetite, and lethargy. [6]
A retrospective database study in Denmark analyzed 15 years of data and found that infants born to mothers who took macrolide antibiotics in the first 13 days postpartum had a 3.5-fold increased risk of neonatal hypertrophic pyloric stenosis, but this was not observed after subsequent use. The proportion of breastfed infants is unknown, but likely high. The proportion of women taking each macrolide antibiotic was also not reported. [7]
In a telephone follow-up study, of the 17 infants whose mothers took erythromycin while breastfeeding, 2 infants experienced diarrhea and 2 infants experienced irritability. None of the reactions required medical attention. [8]
Two meta-analyses failed to confirm an association between maternal use of macrolide antibiotics during lactation and hypertrophic pyloric stenosis in infants. [9][10]
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Interactions
A 77-year-old woman reportedly received 7.5 mg warfarin daily as maintenance therapy and 500 mg erythromycin stearate orally four times daily, resulting in a prothrombin time of 64 seconds (compared to 11 seconds in the control group).

[1]. Erythromycin. Med Clin North Am. 1982 Jan;66(1):79-89.

[2]. Activity of azithromycin or erythromycin in combination with antimalarial drugs against multidrug-resistant Plasmodium falciparum in vitro. Acta Trop. 2006 Dec;100(3):185-91. Epub 2006 Nov 28.

[3]. Antitumor Effect of Erythromycin in Mice. Chemotherapy.

[4]. Neuroprotective effects of erythromycin on cerebral ischemia reperfusion-injury and cell viability after oxygen-glucose deprivation in cultured neuronal cells. Brain Res. 2014 Nov 7. 1588:159-67.

Erythromycin stearate is a fluffy, colorless powder or a fine white powder. (NTP, 1992)
Erythromycin stearate is an aminoglycoside antibiotic.
Erythromycin stearate is the stearate form of erythromycin, a broad-spectrum topical macrolide antibiotic with antibacterial activity. Erythromycin stearate diffuses across the bacterial cell membrane and reversibly binds to the 50S subunit of the bacterial ribosome, thereby inhibiting bacterial protein synthesis. The action of erythromycin stearate may be bacteriostatic or bactericidal, depending on the drug concentration at the site of infection and the sensitivity of the associated microorganism.
See also: Erythromycin (containing the active moiety).

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Mechanism of Action
…Inhibits protein synthesis by binding to the 50S ribosomal subunit of susceptible microorganisms. …The binding of erythromycin to the ribosome is reversible, but only occurs when the 50S subunit dissociates from the tRNA molecule carrying the nascent peptide chain. The production of highly polymerized homopeptides is inhibited. Erythromycin
The non-ionized form of this drug has significantly higher cell permeability, which may explain the enhanced antibacterial activity observed at alkaline pH. Erythromycin/
Therapeutic Uses

Its effects and uses are the same as erythromycin.
Erythromycin can be used for disseminated gonorrhea in pregnant women allergic to penicillin…13 patients…received 500 mg of erythromycin stearate…orally every 6 hours for 5 days, showing rapid clinical and bacteriological responses.
Antibacterial Agent
Veterinary Drug: Antibacterial Agent
Drug Warnings

…Erythromycin and its derivatives rarely cause serious adverse reactions.

C55H103NO15

1018.40

1003.717

643-22-1

Erythromycin;114-07-8;Erythromycin lactobionate;3847-29-8;Erythromycin (aspartate);30010-41-4;Erythromycin thiocyanate;7704-67-8;Erythromycin A dihydrate;59319-72-1

12559

CRYSTALS
WHITE OR SLIGHTLY YELLOW CRYSTALS OR POWDER

1.112g/cm3

77-79ºC

523.101ºC

1.518

8.118

6

16

23

71

1380

18

CC[C@@H]1[C@](C)([C@@H]([C@@H](C)C(=O)[C@H](C)C[C@](C)([C@@H]([C@@H](C)[C@@H]([C@@H](C)C(=O)O1)O[C@H]2C[C@](C)([C@H]([C@H](C)O2)O)OC)O[C@H]3[C@@H]([C@H](C[C@@H](C)O3)N(C)C)O)O)O)O.CCCCCCCCCCCCCCCCCC(=O)O

YAVZHCFFUATPRK-YZPBMOCRSA-N

InChI=1S/C37H67NO13.C18H36O2/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26;1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3;2-17H2,1H3,(H,19,20)/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-;/m1./s1

(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione;octadecanoic acid

2942000000

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.)