Glucocorticoids; Anti~inflammatory steroid

Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There, these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to the synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2 and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators, including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase.

Absorption, Distribution and Excretion
A strong correlation exists between the dissolution rates of the dissolved and undissolved phases of fluprednisolone and the dissolution rate of the implanted particles in rats. It binds primarily in the liver, but also in the kidneys (human, oral).

Interactions
Systemic effects of administered corticosteroids, including dexamethasone, may be reduced when taken with high doses of barbiturates. Although no documented reports exist, fluprednisolone may also interact with phenobarbital in a similar manner.
Phenytoin is known to increase the metabolism of hydrocortisone in humans, and it is likely that fluprednisolone would interact similarly.
The effect of glucocorticoids on oral anticoagulant therapy is variable—both enhancement and reduction of anticoagulant efficacy have been reported with concurrent use. Patients receiving glucocorticoids along with oral anticoagulants should be monitored (e.g., via coagulation indices) to ensure the desired anticoagulant effect is maintained. /Corticosteroids/
Because corticosteroids suppress antibody response, they may reduce the effectiveness of toxoids and live or inactivated vaccines. They may also promote replication of certain organisms in live, attenuated vaccines, and at supraphysiologic doses, can worsen neurological reactions to some vaccines. Routine vaccination should generally be postponed until corticosteroid therapy is discontinued. Administration of live or live, attenuated vaccines—including smallpox vaccine—is contraindicated in patients receiving immunosuppressive doses of glucocorticoids. In such patients, inactivated vaccines may not elicit the expected antibody response.
According to the Public Health Service Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP), live virus vaccines are usually not contraindicated in patients receiving corticosteroids under the following conditions: short-term therapy (less than 2 weeks), low to moderate doses, long-term alternate-day therapy with short-acting preparations, maintenance physiologic (replacement) doses, or topical, ophthalmic, intra-articular, bursal, or tendon injections. If immunization is necessary during corticosteroid therapy, serologic testing may be required to confirm adequate antibody response, and additional vaccine or toxoid doses may be needed. Immunization can proceed in patients receiving nonimmunosuppressive doses of glucocorticoids or those on replacement therapy (e.g., for Addison's disease). /Corticosteroids/

Antidote and Emergency Treatment
/SRP:/ Immediate first aid: Ensure proper decontamination. If the patient is not breathing, begin artificial respiration using a demand valve resuscitator, bag-valve-mask device, or pocket mask as trained. Perform CPR if needed. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, position the patient forward or on their left side (head-down if possible) to maintain airway patency and prevent aspiration. Keep the patient calm and maintain normal body temperature. Seek medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a clear airway (using an oropharyngeal or nasopharyngeal airway if necessary). Suction as needed. Monitor for respiratory distress and assist ventilation if required. Administer oxygen via non-rebreather mask at 10–15 L/min. Watch for signs of pulmonary edema and treat accordingly. Monitor for shock and manage if it develops. Anticipate and treat seizures if they occur. For eye exposure, irrigate immediately with water and continue with 0.9% saline during transport. Do not use emetics. If the patient is alert, has a strong gag reflex, and is not drooling, rinse the mouth and give up to 200 mL of water (5 mL/kg) for dilution. After decontamination, cover skin burns with dry sterile dressings. /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway management in unconscious patients or those with severe pulmonary edema or respiratory distress. Positive-pressure ventilation with a bag-valve-mask device may be helpful. Pharmacologic therapy may be considered for pulmonary edema. For severe bronchospasm, consider a beta agonist such as albuterol. Monitor cardiac rhythm and manage arrhythmias as needed. Start an IV of D5W at a minimal rate to keep the vein open. Use 0.9% saline or lactated Ringer’s if hypovolemia is suspected. In case of hypotension with signs of hypovolemia, administer fluids cautiously and watch for fluid overload. Treat seizures with diazepam or lorazepam. Proparacaine hydrochloride may be used to facilitate eye irrigation. /Poisons A and B/

Human Toxicity Excerpts
/SIGNS AND SYMPTOMS/ Glucocorticoids may cause fetal harm when used during pregnancy. In a retrospective study of 260 women who received pharmacological doses of glucocorticoids while pregnant, there were 2 cases of cleft palate, 8 stillbirths, 1 spontaneous abortion, and 15 premature births. Another study reported 2 cleft palate cases among 86 births. Although these rates are higher than those in the general population, they may also reflect the effects of underlying maternal illness. Additional fetal abnormalities linked to glucocorticoid use during pregnancy include hydrocephalus and gastroschisis. Women should be advised to inform their healthcare provider if they become or plan to become pregnant while on glucocorticoids. If use during pregnancy is necessary or if pregnancy occurs during treatment, the potential risks should be carefully evaluated. /Corticosteroids/

[1]. https://pubchem.ncbi.nlm.nih.gov/compound/5876

6α-Fluorprednisolone is a fluorinated steroid. A synthetic glucocorticoid with anti-inflammatory properties. Mechanism of Action: Glucocorticoids inhibit inflammatory processes through multiple pathways. They interact with specific intracellular receptor proteins in target tissues, thereby altering the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cytoplasm bind to steroid ligands to form hormone-receptor complexes, which eventually translocate to the nucleus. In the nucleus, these complexes bind to specific DNA sequences and alter their expression. These complexes may induce mRNA transcription, leading to the synthesis of new proteins. These proteins include lipocortin, which is known to inhibit PLA2a, thereby blocking the synthesis of prostaglandins, leukotrienes, and platelet-activating factor (PAF). Glucocorticoids also inhibit the production of other mediators, including arachidonic acid metabolites (such as cyclooxygenase), cytokines, interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/

C21H27FO5

378.43

378.184

C, 66.65; H, 7.19; F, 5.02; O, 21.14

53-34-9

5876

WHITE TO OFF-WHITE POWDER
Crystals

1.35 g/cm3

572.3ºC at 760 mmHg

208 - 213ºC

299.9ºC

1.597

1.505

3

6

2

27

760

8

C[C@@]12[C@H]3[C@H](C[C@@]4([C@](C(CO)=O)(O)CC[C@H]4[C@@H]3C[C@H](F)C1=CC(=O)C=C2)C)O

MYYIMZRZXIQBGI-HVIRSNARSA-N

InChI=1S/C21H27FO5/c1-19-5-3-11(24)7-14(19)15(22)8-12-13-4-6-21(27,17(26)10-23)20(13,2)9-16(25)18(12)19/h3,5,7,12-13,15-16,18,23,25,27H,4,6,8-10H2,1-2H3/t12-,13-,15-,16-,18+,19-,20-,21-/m0/s1

(6S,8S,9S,10R,11S,13S,14S,17R)-6-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-one

fluprednisolone; 53-34-9; Fluprednisolone; NSC-47439; Isopredon; 6alpha-Fluoroprednisolone; Fluprednisolonum; Fluprednisolona; NSC 47439; NSC47439; Alphadrol; Etadrol; Vladicort;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ~125 mg/mL (~330.31 mM)

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.)