Prednisone

Absorption

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.

Toxicity

Data regarding acute overdoses of prednisone are rare but prolonged high doses of prednisone can lead to a higher incidence and severity of adverse effects such as mental symptoms, moon face, abnormal fat deposits, fluid retention, excessive appetite, weight gain, hypertrichosis, acne, striae, ecchymosis, increased sweating, pigmentation, dry scaly skin, thinning scalp hair, increased blood pressure, tachycardia, thrombophlebitis, decreased resistance to infection, negative nitrogen balance with delayed bone and wound healing, headache, weakness, menstrual disorders, accentuated menopausal symptoms, neuropathy, fractures, osteoporosis, peptic ulcer, decreased glucose tolerance, hypokalemia, and adrenal insufficiency.

Description

Cortisone (shown) and its close cousin prednisone (with an additional double bond) are widely used anti-inflammatory agents, but their use must be monitored carefully because they can suppress the immune system. Cortisone was identified in the 1930s by Edward C. Kendall at the Mayo Clinic, who shared the 1950 Nobel Prize for physiology or medicine for his work. Prednisone was developed in the 1950s by Arthur Nobile and co-workers at Schering.

Chemical properties

White or almost white, crystalline powder.

The Uses of Prednisone

Prednisone is used for the same indications as cortisone for inflammatory processes, allergies, and adrenal gland insufficiency; however, it is somewhat more active than cortisone and has less of an effect on mineral volume.

The Uses of Prednisone

Adrenocortical steroid. Glucocorticoid, antiinflammatory.

The Uses of Prednisone

Downregulates TNF-α production and NF-κB expression

Background

A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver.
Prednisone was granted FDA approval on 21 February 1955.

Indications

Prednisone is indicated as an anti-inflammatory or immunosuppressive drug for allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, infectious, endocrine, or neoplastic conditions as well as in organ transplant.

What are the applications of Application

Prednisone is downregulates TNF-α production and NF-κB expression

Definition

ChEBI: A synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. Prednisone is a prodrug that is converted by the liver into prednisolone (a beta-hydroxy group instead f the oxo group at position 11), which is the active drug and also a steroid.

Indications

Prednisone 2.5 to 7.5 mg, administered at night or dexamethasone 0.25 to 0.75 mg are useful in female patients, with severe acne unresponsive to conventional therapy, who suffer from adrenal gland overproduction of androgens such as congenital adrenal hyperplasia.

brand name

Cortan (Halsey); Delta-Dome (Bayer); Deltasone (Pharmacia & Upjohn); Liquid Pred (Muro); Meticorten (Schering); Orasone (Solvay Pharmaceuticals); Paracort (Parke-Davis).

General Description

Odorless white crystalline powder.

General Description

Prednisone, Δ¹-cortisone, 17,21-dihydroxypregna-1,4-diene-3,11,20-trione, has systemic activityvery similar to that of prednisolone, and because of itslower salt-retention activity, it is often preferred over cortisoneor hydrocortisone. Prednisone must be reduced in vivoto prednisolone to provide the active GC.

Air & Water Reactions

Very slightly water soluble .

Hazard

Questionable carcinogen.

Pharmacokinetics

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.

Safety Profile

Poison by intraperitoneal and subcutaneous routes. Moderately toxic by intramuscular route. Human systemic effects: sensory change involving peripheral nerves, dermatitis. Experimental reproductive effects. Questionable carcinogen with experimental tumorigenic data. Mutation data reported. Has been implicated in aplastic anemia.

Synthesis

Prednisone is 17|á,21-dihydroxypregna-1,4-dien-3,11-20-trione (27.1.31). Prednisone differs from cortisone in the presence of an additional double bond between C1 and C2. There are various ways of synthesizing it. In one of these, as is in the case when synthesizing cortisone, it is synthesized from dihydrocortisone acetate. However, in the given example, this compound undergoes dibromination by molecular bromine, giving 2,4-dibromo-derivative of dihydrocortisone 27.1.30. Dehydrobromination with 3,5-lutidine, followed by subsequent hydrolysis of the acetyl group using potassium bicarbonate gives the desired prednisone (27.1.31). Prednisone is also synthesized by microbiological dehydrogenation of cortisone.

Metabolism

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.

Purification Methods

Crystallise prednisone from acetone/hexane, then recrystallise it from Me2CO. The monoacetate crystallises from Me2CO/hexane with m 227-233o(dec), [] D +186o (c 1, dioxane), and the diacetate crystallises from 25Me2CO/hexane with m 219-221o(dec), [] D +125o (c 1, CHCl3). [Hertzog et al. Tetrahedron 18 581 1962, Beilstein 8 IV 3531.]