プレドニゾン

1.46

log Kow = 1.46

0.6

Crystals

White to practically white, crystalline powder

Very slightly soluble (NTP, 1992)

Very slightly soluble

Very slightly soluble in water; 1 g soluble in 150 mL alcohol, in 200 mL chloroform; slightly soluble in methanol

1.11e-01 g/L

Hazardous decomposition products formed under fire conditions - Carbon oxides.

When heated to decomposition it emits acrid smoke and irritating fumes.

451 to 455 °F (DEC) (NTP, 1992)

230

234 °C (decomposes)

233 - 235 °C

Prednisone is an odorless white crystalline powder. (NTP, 1992)

Solid

253.9 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID4021185]；184.1 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID4021185]；192.2 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID4021185]

181.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

174.8 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；180.52 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

180.1 Ų [M+H]+ [CCS Type: TW]

Danger

H360 (33.7%): May damage fertility or the unborn child [Danger Reproductive toxicity]；H361 (65.1%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]；H372 (32%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]；H373 (20.1%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P203, P260, P264, P270, P280, P318, P319, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 169 reports by companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including prednisone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Prednisone is included on this list.

Implantation or injectable dosage form new animal drugs. Sterile prednisone suspension. ... Indications for use: It is used /in horses, dogs and cats/ for conditions requiring an anti-inflammatory agent. ... Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.；SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.；INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.；INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Keep container tightly closed in a dry and well-ventilated place.

Prednisone tablets should be stored in well closed containers at a temperature less than 40 °C, preferably between 15-30 °C. Prednisone syrup should be stored in tight containers. Prednisone oral solution and oral concentrate solution should be stored in tight containers at 15-30 °C.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should keep this material in a tightly-closed container under an inert atmosphere, and store it in a freezer. (NTP, 1992)

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter.；RECOMMENDED GLOVE MATERIALS: Permeation data indicate that neoprene gloves may provide protection to contact with this compound. Neoprene over latex gloves is recommended. However, if this chemical makes direct contact with your gloves, or if a tear, puncture or hole develops, remove them at once. (NTP, 1992)

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Concomitant use of anticholinesterase agents (e.g., neostigmine, pyridostigmine) and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. If concomitant therapy must occur, it should take place under close supervision and the need for respiratory support should be anticipated. /Corticosteroids/

Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect. /Corticosteroids/

Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required. /Corticosteroids/

Cholestyramine may increase the clearance of corticosteroids. /Corticosteroids/

For more Interactions (Complete) data for PREDNISONE (25 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 110(SRC), determined from a structure estimation method(2), indicates that prednisone is expected to have high mobility in soil(SRC). Volatilization of prednisone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.8X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Prednisone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.8X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2016).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 110(SRC), determined from a structure estimation method(2), indicates that prednisone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.8X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 4(SRC), from its log Kow of 1.46(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2016).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), prednisone, which has an estimated vapor pressure of 3.8X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase prednisone may be removed from the air by wet and dry deposition(SRC). Prednisone contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Adverse effects are common in patients receiving glucocorticoids in high doses or over a long period. Regimens involving prednisone administration of ≥40 mg daily are considered "high-dose." The primary adverse effects associated with prednisone therapy include hyperglycemia, insomnia, increased appetite, hypertension, osteoporosis, edema, adrenal suppression, cataracts, delayed wound healing, skin fragility, weight gain, increased risk of infections, and fractures. Potential cardiovascular and metabolic effects include hypertension, hyperglycemia, and dyslipidemia.；Other adverse reactions include adrenal insufficiency, particularly for patients with sepsis or undergoing stressful procedures; this is typically diagnosable when the patient is hypotensive and not responsive to fluids, vasopressors, or cardiogenic medications. Once adrenal insufficiency is suspected, treatment should be initiated immediately with a dose of 100 mg of hydrocortisone every 8 hours. Osteonecrosis of the femoral head has also been reported.；Drug-Drug Interactions；* Amphotericin B: Prednisone combined with amphotericin B or other potassium-lowering drugs may cause hypokalemia. Therefore, clinicians are advised to monitor electrolyte levels in patients receiving these medications.；* Macrolides: Some macrolide antibiotics (eg, clarithromycin) may slow the breakdown of prednisone, leading to increased steroid levels.；* Warfarin: When warfarin is taken with prednisone, the former's anticoagulant effects can become inconsistent. Frequent INR checks are recommended.；* Isoniazid: Isoniazid levels may drop when given with prednisone, which might lower its effectiveness.；* Bupropion: Combining prednisone with bupropion may increase seizure risk. If used together, doses should start low and increase slowly.；* Cholestyramine: Cholestyramine may reduce how long prednisone stays active by increasing its elimination rate.；* Cyclosporine: When prednisone and cyclosporine are used together, the risk of immunosuppression increases.；* Digoxin: Individuals receiving digoxin could be more prone to abnormal heart rhythms if potassium levels fall due to steroid therapy.；* Estrogens: Estrogens can slow prednisone metabolism, leading to prolonged steroid action.；* Fluoroquinolones: Tendon injuries, including ruptures, have been reported in patients receiving fluoroquinolones like ciprofloxacin together with prednisone, especially in older adults.；* CYP3A4 inducers/inhibitors: Drugs that increase CYP3A4 enzyme activity (eg, phenytoin or rifampin) can make prednisone less effective. On the flip side, CYP3A4 inhibitors (like ketoconazole) may increase steroid levels and the risk of adverse effects.；* Ketoconazole: Ketoconazole may also hinder natural steroid production, which can lead to problems if prednisone is stopped too quickly.；* NSAIDs: Taking NSAIDs (eg, aspirin) with prednisone increases the risk of stomach ulcers or bleeding.

Readily absorbed from the gastrointestinal tract. Rayos, the delayed-release formulation, has a 4-hour release time. To compare, the delayed-release formulation has a Tmax of 6.0 - 6.5 hours in healthy male subjects, whereas the immediate-release formulation has a Tmax of 2.0 hours. The rate of absorption, Cmax, and exposure is comparable between formulations.

IDENTIFICATION AND USE: Prednisone is white crystalline powder with a persistent bitter after-taste. It is glucocorticoid, anti-inflammatory agent and antineoplastic agent. HUMAN EXPOSURE AND TOXICITY: Prednisone causes profound and varied metabolic effects when used at therapeutic doses, given on a continuous basis. When given in large doses it can induce cardiac complications. In addition, it modifies the body's immune response to diverse stimuli; among the changes that occur are lymphopenia, monocytopenia and suppression of delayed hypersensitivity skin tests. Fluid and electrolyte disturbances may occur, including sodium and fluid retention, which may lead to congestive heart failure and hypertension. With large doses, potassium loss, hypokalemic alkalosis, and increased calcium excretion may occur. Glucocorticoids may cause fetal damage when administered to pregnant women. One retrospective study of 260 women who received pharmacologic dosages of glucocorticoids during pregnancy revealed 2 instances of cleft palate, 8 stillbirths, 1 spontaneous abortion, and 15 premature births. Another study reported 2 cases of cleft palate in 86 births. No chromosomal damage was detected in peripheral lymphocytes of patients treated with 3 mg/kg bw per day prednisone alone for 28 days and then with 0.5-1 mg/kg bw per day for 18-120 months. ANIMAL STUDIES: Carcinogenicity studies have been conducted in rats and mice. Of treated males, 7/20 developed tumors, among which were 3 pituitary tumors and 1 tumor of the breast; 16/18 female rats developed tumors, 8 of the breast, 5 of the pituitary, 2 of the adrenal and 1 of the liver. The overall tumor incidence in females was 1.5-2-fold higher than that in controls. However in mice, the tumor incidence in treated males was 4/19 (21%), with 2 lymphosarcomas and 2 lung tumors, and that in treated females was 8/27 (30%), with 4 lung tumors, 2 lymphosarcomas and 2 uterine tumors. These incidences were not significantly greater than those

Signs and Symptoms of Overdose；Like any anti-inflammatory agent, steroid toxicity is treated similarly to any non-steroidal anti-inflammatory drug overdose or toxicity. Although the frequency of life-threatening complications from steroids and NSAID overdose is low, the overdose response ranges from no symptoms to death despite intensive-care treatment. Most symptoms are due to the excessive pharmacological action of steroids and NSAIDs and include abdominal pain, nausea, vomiting, drowsiness, dizziness, headache, ear ringing, and nystagmus. A significant dose-response relationship occurs with the long-term use of systemic corticosteroids and the development of systemic corticosteroid-related complications for patients with severe asthma, resulting in an increased burden and costs on the healthcare system.；Management of Overdose；Assessment of all organ systems can help identify problems. If necessary, hypertension and salt retention should be treated with salt restriction and diuretics. Gastrointestinal perforation requires surgical intervention. Antibiotics and antifungals should be prescribed for infections. An iatrogenic crushing syndrome caused by a supplement containing dexamethasone has been reported. Gradual tapering of corticosteroids is advisable to prevent adrenal insufficiency. Potent proton pump inhibitors should be prescribed for gastroprotection. Hypokalemia can be treated by replacement. Steroid-induced psychosis can be managed with antipsychotics. Hyperglycemia should be treated with insulin in critically ill patients. After stabilization, patients should be prescribed vitamin D and calcium. Mitotane and ketoconazole decrease cortisol production and should be used only under the supervision of an endocrinologist.

Prednisone is a glucocorticoid receptor agonist. It is first metabolized in the liver to its active form, prednisolone. Prednisolone crosses cell membranes and binds with high affinity to specific cytoplasmic receptors. The result includes inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, suppression of humoral immune responses, and reduction in edema or scar tissue. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Prednisone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension.

/AQUATIC SPECIES/ Solar simulator irradiation of an aqueous suspension of prednisone, a widely prescribed drug, produces seven photochemical derivatives. The compounds have been identified on the basis of their physical features. All the chemicals have been tested to evaluate their toxic effects on freshwater organisms from different trophic levels. The rotifer Brachionus calyciflorus and two crustaceans, the cladoceran Daphnia magna and the anostracan Thamnocephalus platyurus, were used to perform acute toxicity tests. Chronic toxicity tests have been performed on the alga Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum) and the crustacean Ceriodaphnia dubia. The results showed low acute and chronic toxicity of prednisone. Some of the photoproducts had high toxic effects on C. dubia.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of October 28, 2016: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Short-Term Toxicity Studies," "Long-Term Carcinogenicity Studies," and "Genetic Toxicology Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp.niehs.nih.gov/testing/status/agents/ts-10936-e.html]

Prednisone concentration in sewage influent samples in the Ebre, Ter and Llobregat Rivers, Tarragona area, Spain ranged from 21-285 ng/L(1). Prednisone was detected in 23 of 37 water samples collected from the River Wenyu and tributaries, Beijing China between Aug 9-12, 2006 at concentrations ranging from not detected to 0.25 ng/L. No farms or livestock areas were located within the sampling area(2).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of prednisone can be estimated to be 110(SRC). According to a classification scheme(2), this estimated Koc value suggests that prednisone is expected to have high mobility in soil

/SIGNS AND SYMPTOMS/ Prednisone causes profound and varied metabolic effects when used at therapeutic doses, given on a continuous basis. When given in large doses it can induce cardiac complications. In addition, it modifies the body's immune response to diverse stimuli; among the changes that occur are lymphopenia, monocytopenia and suppression of delayed hypersensitivity skin tests. Fluid and electrolyte disturbances may occur, including sodium and fluid retention, which may lead to congestive heart failure and hypertension. With large doses, potassium loss, hypokalemic alkalosis, and increased calcium excretion may occur.

/SIGNS AND SYMPTOMS/ Moderate- to high-dose glucocorticoid therapy is associated with loss of bone and an increased risk of fracture. There also is evidence that long-term, low-dose (e.g., mean of 5.6 mg of prednisone daily) glucocorticoid therapy is associated with a risk of bone loss. Thus, while the American College of Rheumatology (ACR) previously considered patients who received at least 7.5 mg of prednisone (or its equivalent) daily for 6 months or longer to be at risk for glucocorticoid-induced osteoporosis, they currently consider patients receiving or planning to receive at least 5 mg of prednisone daily for 3 months or longer to be at risk for such bone loss. Skeletal wasting is most rapid during the initial 6 months of therapy, and trabecular bone is affected to a greater degree than is cortical bone. The adverse skeletal effects of glucocorticoids appear to be both dose and duration dependent, with prednisone dosages of at least 7.5 mg daily for 6 months or longer often resulting in clinically important bone loss and increased fracture risk.

/SIGNS AND SYMPTOMS/ Children with acute lymphoblastic leukemia (ALL) receive as part of induction therapy a 4-week course of high-dose glucocorticoid, which is either abruptly discontinued or shortly tapered. The aim of this study was to evaluate the signs and symptoms of steroid withdrawal syndrome and performance status (according to Lansky scale) during the 9-day tapering period and 1 week after withdrawal of the steroid in 63 children randomly allocated to receive prednisone or dexamethasone as part of induction treatment according the AIEOP ALL 2000 protocol. Twenty of 28 (75%) patients on dexamethasone versus 18 of 35 (51.4%) on prednisone (P < 0.05) developed at least one steroid withdrawal symptom during the study period. Three or more symptoms were observed in 39.3% (11/28) of the dexamethasone group and 8.6% (3/35) of the prednisone group (P < 0.05). Dexamethasone patients developed clinical signs earlier (within 3 days from the steroid tapering) than symptomatic prednisone patients. In the prednisone group, the symptoms were less severe and the performance status was higher (P < 0.05). ...

/SIGNS AND SYMPTOMS/ Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection. Infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections in any organ system, may be associated with glucocorticoids alone or in combination with other immunosuppressive agents. These infections may be mild, but they can be severe or fatal, and localized infections may disseminate. Patients who become immunosuppressed while receiving glucocorticoids have increased susceptibility to infections compared with healthy individuals. Some infections such as varicella (chickenpox) and measles can have a more serious or even fatal outcome in such patients, particularly in children. /Corticosteroids/

For more Human Toxicity Excerpts (Complete) data for PREDNISONE (21 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including prednisone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Prednisone is included on this list.

Implantation or injectable dosage form new animal drugs. Sterile prednisone suspension. ... Indications for use: It is used /in horses, dogs and cats/ for conditions requiring an anti-inflammatory agent. ... Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

A - Alimentary tract and metabolism；A07 - Antidiarrheals, intestinal antiinflammatory/antiinfective agents；A07E - Intestinal antiinflammatory agents；A07EA - Corticosteroids acting locally；A07EA03 - Prednisone

H - Systemic hormonal preparations, excl. sex hormones and insulins；H02 - Corticosteroids for systemic use；H02A - Corticosteroids for systemic use, plain；H02AB - Glucocorticoids；H02AB07 - Prednisone

QA - Alimentary tract and metabolism；QA07 - Antidiarrheals, intestinal anti-inflammatory/antiinfective agents；QA07E - Intestinal antiinflammatory agents；QA07EA - Corticosteroids acting locally；QA07EA03 - Prednisone

QH - Systemic hormonal preparations, excl. sex hormones and insulin；QH02 - Corticosteroids for systemic use；QH02A - Corticosteroids for systemic use, plain；QH02AB - Glucocorticoids；QH02AB07 - Prednisone

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisone has a short duration of action as the half life is 2-3 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Prednisone is first metabolized in the liver to its active form, prednisolone, a glucocorticoid agonist corticosteroid. The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

In physiologic doses, corticosteroids are administered to replace deficient endogenous hormones. In larger (pharmacologic) doses, glucocorticoids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. The drugs suppress the immune response by reducing activity and volume of the lymphatic system, producing lymphocytopenia, decreasing immunoglobulin and complement concentrations, decreasing passage of immune complexes through basement membranes, and possibly by depressing reactivity of tissue to antigen-antibody interactions. Glucocorticoids stimulate erythroid cells of bone marrow, prolong survival time of erythrocytes and platelets, and produce neutrophilia and eosinopenia. Glucocorticoids promote gluconeogenesis, redistribution of fat from peripheral to central areas of the body, and protein catabolism, which results in negative nitrogen balance. They reduce intestinal absorption and increase renal excretion of calcium. /Corticosteroids/

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 synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a 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. /Glucocorticoids/

Prednisone and its active metabolite [prednisolone] have half lives of 2-3 hours from both immediate and delayed release preparations.

In a series of 22 normal subjects, the mean peak serum concentration was 930 ug/L (range, 508-1579) following oral administration of a 50 mg tablet. The overall mean serum half-life was 2.95 hours

Prednisone is metabolized to 17α,21-dihydroxy-pregnan-1,4,6-trien-3,11,30-trione (M-XVII), 20α-dihydro-prednisone (M-V), 6βhydroxy-prednisone (M-XII), 6α-hydroxy-prednisone (M-XIII), or 20β-dihydro-prednisone (M-IV). 20β-dihydro-prednisone is metabolized to 17α,20ξ,21-trihydroxy-5ξ-pregn-1-en-3,11-dione(M-XVIII). Prednison is reversibly metabolized to [prednisolone]. Prednisolone is metabolized to Δ6-prednisolone (M-XI), 20α-dihydro-prednisolone (M-III), 20β-dihydro-prednisolone (M-II), 6αhydroxy-prednisolone (M-VII), or 6βhydroxy-prednisolone(M-VI). 6αhydroxy-prednisolone is metabolized to 6α,11β,17α,20β,21-pentahydroxypregnan-1,4-diene-3-one (M-X). 6βhydroxy-prednisolone is metabolized to 6β,11β,17α,20β,21-pentahydroxypregnan-1,4-diene-3-one (M-VIII), 6β,11β,17α,20α,21-pentahydroxypregnan-1,4-diene-3-one (M-IX), and 6β,11β,17α,21-tetrahydroxy-5ξ-pregn-1-en-3,20-dione (M-XIV). MVIII is metabolized to 6β,11β,17α,20β,21-pentahydroxy-5ξ-pregn-1-en-3-one (M-XV) and then to MXIV, while MIX is metabolized to 6β,11β,17α,20α,21-pentahydroxy-5ξ-pregn-1-en-3-one (M-XVI) and then to MXIV. These metabolites and their glucuronide conjugates are excreted predominantly in the urine.

In one study after an oral dose of prednisone, the plasma prednisolone concentration peaked between 60 and 120 min and then declined exponentially. After rapid iv injection of steroid, the plasma prednisolone concentration peaked within 10 to 20 min. An initial rapid distribution phase succeeded by a slower decay phase was expressed by a biphasic exponential disappearance curve of the plasma prednisolone concentration versus time. Plasma prednisolone concentrations achieved with an oral dose of prednisone were in the same range as those obtained during the second phase after iv administration.

Reduction of the 11-oxo to the 11alpha-hydroxyl group by the enzyme 11beta-hydroxydehydrogenase converts prednisone to prednisolone, its biologically active form. This reaction takes place mainly in the liver, and may proceed satisfactorily even in the presence of liver disease

In vitro, prednisone is converted to prednisolone by liver, lung and renal tissue. Conversely, prednisolone is converted to prednisone by renal tissue.

... The aim of this work was to evaluate the effects of these corticosteroids on the expression of several forms of cytochromes p450, including p450 1A2, 2D6, 2E1, and 3A, and on cyclosporin A oxidase activity in human liver. For this purpose, human hepatocytes prepared from lobectomies were maintained in culture in a serum-free medium, in collagen-coated dishes, for 96-144 hr, in the absence or presence of 50-100 uM corticosteroids, rifampicin, or dexamethasone. To mimic more closely the current clinical protocol, hepatocyte cultures were also co-treated with corticosteroids and cyclosporin A or ketoconazole (a selective inhibitor of cytochromes p450 3A). Cyclosporin A oxidase activity, intracellular retention of cyclosporin A oxidized metabolites within hepatocytes, accumulation of cytochromes p450 proteins and corresponding messages, and de novo synthesis and half-lives of these cytochromes p450 were measured in parallel in these cultures. Our results, obtained from seven different hepatocyte cultures, showed that 1) dexamethasone and prednisone, but not prednisolone or methylprednisolone, were inducers of cytochrome p450 3A, at the level of protein and mRNA accumulation, as well as of cyclosporin A oxidase activity, known to be predominantly catalyzed by these cytochromes p450; 2) although corticosteroids are known to be metabolized in human liver, notably by cytochrome p450 3A, partial or total inhibition of this cytochromes p450 by cyclosporin or ketoconazole, respectively, did not affect the inducing efficiency of these molecules; 3) corticosteroids did not affect the half-life of cytochrome p450 3A or the accumulation of other forms of cytochromes p450, including 1A2, 2D6, and 2E1; 4) chronic treatment of cells with cyclosporin did not affect cytochrome p450 3A accumulation; 5) corticosteroids were all competitive inhibitors of cyclosporin A oxidase in human liver microsomes, with Ki values of 61 + or - 12, 125 + or - 25, 190 + or - 38, and 210 + or - 42 uM

Prednisone is completely converted to the active metabolite prednisolone by 11‘_-hydroxysteroid dehydrogenases. It is then further metabolized mainly in the liver. The exposure of prednisolone is 4-6 fold higher than that of prednisone. Route of Elimination: Excreted in the urine as sulfate and glucuronide conjugates. Half Life: Half life of both the immediate- and delayed- release formulation is 2 to 3 hours.

3EN3HG4WSW

PREDNISONE ANHYDROUS

Established Pharmacologic Class [EPC] - Corticosteroid

Mechanisms of Action [MoA] - Corticosteroid Hormone Receptor Agonists

Prednisone anhydrous is a Corticosteroid. The mechanism of action of prednisone anhydrous is as a Corticosteroid Hormone Receptor Agonist.

VB0R961HZT

Substances that reduce or suppress INFLAMMATION.

A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)

Oral prednisone has a Tmax of 2 hours, while the delayed-release formulation has a Tmax of 6-6.5 hours. A 5mg dose of prednisone has an AUC of 572mL/min/1.73m2, a 20mg dose of prednisone has an AUC of 1034mL/min/1.73m2, and a 50mg dose of prednisone has an AUC of 2271mL/min/1.73m2. Data regarding the Cmax of prednisone is not readily available.

Prednisone is excreted mainly in the urine as sulfate and glucuronide conjugates.

Data regarding the volume of distribution for prednisone is not readily available. However, a 0.15mg/kg dose of prednisolone has a volume of distribution of 29.3L, while a 0.30mg/kg dose has a volume of distribution of 44.2L.

Data regarding the clearance of prednisone is not readily available. A 5.5µg/h/kg infusion of prednisolone has an average clearance of 0.066±0.12L/h/kg, while a 0.15±0.03L/h/kg infusion has an average clearance of 0.15L/h/kg.

Thirty minutes after iv administration of (3)H-prednisone to a monkey, the concentration of prednisone was highest in the kidney. The drug was also found in the liver, spleen, lung, small intestine, serum and bile. The concentration of prednisolone was highest in the liver. It was also found in the kidney, pancreas, spleen, lung, small intestine, serum and bile.

Prednisone is readily absorbed from the gut. Serum concentrations of prednisone and prednisolone, its active metabolite, have been found to be maximal 1 hour after oral administration of a 5-mg tablet of prednisone to beagle dogs. Following both ip and oral administration of prednisone to mice, serum levels of prednisone, prednisolone and other metabolites were maximal at 15 min. These levels were higher in mice given ip injections of prednisone than in those receiving the same doses by the oral route. Oral administration of prednisone to dogs and monkeys led to serum levels comparable with those following iv injections, but individual variations were relatively large.

MEDICATION

MEDICATION (VET)

Anti-Inflammatory Agents; Antineoplastic Agents, Hormonal; Glucocorticoids

Use (kg) in Switzerland (2009): >100；Use (kg; approx.) in Germany (2009): >500；Use (kg) in USA (2002): 8040；Use (kg) in France (2004): 1550；Consumption (g per capita) in Switzerland (2009): 0.013；Consumption (g per capita; approx.) in Germany (2009): 0.0061；Consumption (g per capita) in the USA (2002): 0.029；Consumption (g per capita) in France (2004): 0.026；Excretion rate: 1；Calculated removal (%): 45.8

For the treatment of drug-induced allergic reactions, perennial or seasonal allergic rhinitis, serum sickness, giant cell arteritis acute rheumatic or nonrheumatic carditis, systemic dermatomyositis, systemic lupus erythematosus, atopic dermatitis, contact dermatitis, exfoliative dermatitis, bullous dermatitis herpetiformis, severe seborrheic dermatitis, severe (Stevens-Johnson syndrome) erythema multiforme, mycosis fungoides, pemphigus, severe psoriasis, acute adrenocortical insufficiency, Addison's disease, secondary adrenocortical insufficiency, congenital adrenal hyperplasia, hypercalcemia associated with neoplasms, nonsuppurative thyroiditis, ulceratice colitis, Crohn's disease, acquired hemolytic anemia, congenital hypoplastic anemia, erythroblastopenia, adult secondary thrombocytopenia, adult idiopathic thrombocytopenia purpura, acute or subacute bursitis, epicondylitis, acute nonspecific tenosynovitis, acute or chronic lymphocytic leukemia, Hodgkin's or non-Hodgkin's lynphomas, Waldenstrom's macroglobulinemia, primary brain tumors (adjunct), nephrotic syndrome, tuberculous meningitis, multiple sclerosis, myasthenia gravis. cerebral edema, chorioretinitis, diffuse posterior choroiditis, aleergic conjunctivitis, Herpes zoster ophthalmicus, anterior segment inflammation, iridocyclitis, iritis, keratitis, optoc neuritis, sympathetic ophthalmia, corneal marginal allergic ulcers, symptomatic sarcoidosis, Loeffler's syndrome not manageable by other means, berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy and aspiration pneumonitis.

Chemical synthesis of prednisone was first reported by introduction of the two double bonds in ring A by 2,4-dibromination of the 3-ketone and dehydrobromination, but the yields were only 10-15%. Prednisone is prepared more efficiently microbiologically by the dehydrogenation of cortisone: a pure culture of Corynebacterium simplex is grown in a sterilized nutrient medium of yeast extract, and cortisone is added. The C. simplex selectively dehydrogenates the cortisone. When the reaction is complete, the fermentation broth is extracted and purified to give prednisone in good yield.

Preparation: Oliveto, Gould, United States of America patent 2897216 (1959 to Schering); Microbiological preparation: ... Nobile, United States of America patents 2837464 and 3134718 (1958, 1964 both to Shering).

Prednisolone (alcohol oxidation)

Oral: 1 mg, 2 mg, 5 mg, Rayos

Table: Prednisone Preparations [Table#4483]

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Pharmaceuticals

Pharmaceuticals -> Alimentary tract and metabolism -> Glucocorticoides

Pregna-1,4-diene-3,11,20-trione, 17,21-dihydroxy-: INACTIVE

Generic name for an analog of cortisone.

Solar simulator irradiation of an aqueous suspension of prednisone, a widely prescribed drug, produces seven photochemical derivatives. ...