Prednisone (intramuscular injection, 10 mg/kg once daily, on days 4–13) lowers the survival rate in BALB/c mice with encephalomyocarditis virus myocarditis on days when compared to the control group. In addition, myocardial virus titers peak on day 4, but no antibody titer is present. On day 8, both the virus and antibody titers are still elevated. Day 10 antibody titers are still significantly elevated compared to controls, but viral titers are significantly lower[2]. In the SLE mouse (MRL/lpr) model, prednisone (5 mg/kg, administered intragastrially, once daily) can alter the metabolism of FA[3].

Animal/Disease Models: Female MRL/lpr mice[3]
Doses: 5 mg/kg
Route of Administration: intragastrically (po) administration, daily
Experimental Results: Elevated polyunsaturated FA, such as arachidonic acid and docosahexaenoic acid, and decreased the total level of n-6 polyunsaturated fatty acids in.

Absorption, Distribution and Excretion
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.
Prednisone is readily absorbed from the gut. 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 protein binding characteristics of prednisone and prednisolone, alone and together, in human and rabbit plasma and human serum albumin, are reported. The kinetics of prednisolone binding were nonlinear and those of prednisone were linear in both human and rabbit plasma; prednisone binding was linear with human serum albumin, although to a lesser degree. It is suggested that prednisone binds to proteins other than albumin in plasma. Binding of prednisone was not influenced by prednisolone. The results support the hypothesis that the protein binding characteristics of prednisone and prednisolone do not explain the reported nonlinear pharmacokinetics of prednisone.
Administration of physiologic doses unlikely to adversely affect infant. FDA Category: C (C = Studies in laboratory animals have revealed adverse effects on the fetus (teratogenic, embryocidal, etc.) but there are no controlled studies in pregnant women. The benefits from use of the drug in pregnant women may be acceptable despite its potential risks, or there are no laboratory animal studies or adequate studies in pregnant women.) /Adrenocorticosteroids/ /from table II/

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Metabolism / Metabolites
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 for dexamethasone, prednisolone, prednisone, and methylprednisolone, respectively; and 6) chronic treatment of cells with corticosteroids did not influence the excretion of oxidized metabolites of cyclosporin from the cells.
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.

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Biological Half-Life
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

Toxicity Summary
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 in controls. Prednisone given to rats from the 11th day of pregnancy until parturition at daily doses of 2.5 or 5 mg was reported to inhibit the growth of the fetal thymus and spleen. Prednisone was not mutagenic in Escherichia coli, and it caused no chromosomal damage when administered to rats. ECOTOXICITY STUDIES: 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 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.
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.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Amounts of prednisone in breastmilk are very low. No adverse effect have been reported in breastfed infants with maternal use of any corticosteroid during breastfeeding. Although it is often recommended to avoid breastfeeding for 4 hours after a dose this maneuver is not necessary because prednisone milk levels are very low. Medium to large doses of corticosteroids given systemically or injected into joints or the breast have been reported to cause temporary reduction of lactation.
◉ Effects in Breastfed Infants
None reported with prednisone or any other corticosteroid. In a prospective follow-up study, six nursing mothers reported taking prednisone (dosage unspecified) with no adverse infant effects.
There are several reports of mothers breastfeeding during long-term use of corticosteroids with no adverse infant effects: prednisone 10 mg daily (2 infants) and prednisolone 5 to 7.5 mg daily (14 infants).
A woman with Crohn's disease used prednisone 60 mg daily in a tapering schedule immediately postpartum during breastfeeding (extent not stated). She also received sulfasalazine 4 grams daily and infliximab 5 mg/kg every 8 weeks during pregnancy and postpartum. At 6 months of age, the infant was asymptomatic with regular weight gain.
The National Transplantation Pregnancy Registry reports that as of December 2013, 124 women with transplants have taken prednisone while breastfeeding 169 infants for periods as long as 48 months, with no apparent infant harm.
◉ Effects on Lactation and Breastmilk
Published information on the effects of prednisone on serum prolactin or on lactation in nursing mothers was not found as of the revision date. Medium to large doses of corticosteroids given systemically or injected into joints or the breast have been reported to cause temporary reduction of lactation.
A study of 46 women who delivered an infant before 34 weeks of gestation found that a course of another corticosteroid (betamethasone, 2 intramuscular injections of 11.4 mg of betamethasone 24 hours apart) given between 3 and 9 days before delivery resulted in delayed lactogenesis II and lower average milk volumes during the 10 days after delivery. Milk volume was not affected if the infant was delivered less than 3 days or more than 10 days after the mother received the corticosteroid. An equivalent dosage regimen of prednisone might have the same effect.
A study of 87 pregnant women found that betamethasone given as above during pregnancy caused a premature stimulation of lactose secretion during pregnancy. Although the increase was statistically significant, the clinical importance appears to be minimal. An equivalent dosage regimen of prednisone might have the same effect.

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Protein Binding
Corticosteroids are generally bound to corticosteroid binding globulin and serum albumin in plasma. Prednisone is <50% bound to protein in plasma.

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Interactions
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.

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Non-Human Toxicity Values
LD50 Mouse im 600 mg/kg
LD50 Mouse sc 101 mg/kg
LD50 Mouse ip 135 mg/kg

[1]. RIEMER AD. Application of the newer corticosteroids to augment diuresis in congestive heart failure. Am J Cardiol. 1958 Apr;1(4):488-96.
[2]. [2]N Tomioka, et al. Effects of prednisolone on acute viral myocarditis in mice. J Am Coll Cardiol. 1986 Apr;7(4):868-72.
[3]. Qianqian Li, et al. Metabolic Profiling Reveals an Abnormal Pattern of Serum Fatty Acids in MRL/lpr Mice Under Treatment With Prednisone. Front Pharmacol. 2020 Feb 25;11:115.

Therapeutic Uses
Anti-Inflammatory Agents; Antineoplastic Agents, Hormonal; Glucocorticoids
Prednisone is usually considered the oral glucocorticoid of choice for anti-inflammatory or immunosuppressant effects. Because it has only minimal mineralocorticoid properties, the drug is inadequate alone for the management of adrenocortical insufficiency. If prednisone is used in the treatment of this condition, concomitant therapy with a mineralocorticoid is also required.
Prednisone tablets and solutions are indicated in the following conditions: Endocrine Disorders: Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice: synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance); congenital adrenal hyperplasia; hypercalcemia associated with cancer; nonsuppurative thyroiditis. /Included in US product label/
Prednisone tablets and solutions are indicated in the following conditions: Rheumatic Disorders: As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: psoriatic arthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy), ankylosing spondylitis, acute and subacute bursitis, acute nonspecific tenosynovitis, acute gouty arthritis, post-traumatic osteoarthritis, synovitis of osteoarthritis, epicondylitis. /Included in US product label/
For more Therapeutic Uses (Complete) data for PREDNISONE (19 total), please visit the HSDB record page.

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Drug Warnings
The profound effects of prednisone on the immune system place patients at increased risk of developing infections of various types. Prednisone may mask some of the signs of infection, and may decrease host resistance and interfere with the ability to localize infections. During prednisone therapy, a polymorphonuclear leukocytosis may develop and may give rise to confusion in the diagnosis of infection. This elevation is dose-related.
Psychiatric reactions have been reported in 4-36% of patients. These disturbances may take various forms, for example, insomnia, changes in mood or psyche, and psychopathies of the manic-depressive or schizophrenic type.
Ophthalmic complications include the development of posterior subcapsular cataracts, and increased intraocular pressure which may lead to glaucoma. In patients with ocular herpes simplex, it may cause corneal perforation.
There are numerous endocrine side effects. Most frequent is development of the Cushingoid state. Fatty deposits in the mediastinum causing mediastinal widening may simulate mediastinal lymphadenopathy. Menstrual irregularities, including amenorrhoea, may occur. There may be secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness. The processes of recovery of normal pituitary and adrenal function require about 1 year in some patients. There may be stunted growth and delayed skeletal maturation in children. Prednisone causes decreased carbohydrate tolerance and may unmask the features of latent diabetes.
For more Drug Warnings (Complete) data for PREDNISONE (38 total), please visit the HSDB record page.

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Pharmacodynamics
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.

C21H26O5

358.43

358.178

53-03-2

Prednisone-d8;Prednisone acetate;125-10-0

5865

Crystals
White to practically white, crystalline powder

1.3±0.1 g/cm3

573.7±50.0 °C at 760 mmHg

236-238 °C(lit.)

314.8±26.6 °C

0.0±3.6 mmHg at 25°C

1.604

1.57

2

5

2

26

764

6

O([H])[C@]1(C(C([H])([H])O[H])=O)C([H])([H])C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])C4=C([H])C(C([H])=C([H])[C@]4(C([H])([H])[H])[C@@]3([H])C(C([H])([H])[C@@]21C([H])([H])[H])=O)=O

XOFYZVNMUHMLCC-ZPOLXVRWSA-N

InChI=1S/C21H26O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h5,7,9,14-15,18,22,26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1

(8S,9S,10R,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,9,12,14,15,16-octahydrocyclopenta[a]phenanthrene-3,11-dione

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)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.80 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), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (5.80 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 20.8 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: ≥ 2.08 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)