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a salt or ester of acetic acid (同)ethanoate
a glucocorticoid (trade names Pediapred or Prelone) used to treat inflammatory conditions (同)Pediapred, Prelone

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/15 15:12:14」(JST)

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Prednisolone is a synthetic glucocorticoid, a derivative of cortisol, which is used to treat a variety of inflammatory and auto-immune conditions. It is the active metabolite of the drug prednisone^[1] and is used especially in patients with liver failure, as these individuals are unable to metabolise prednisone into prednisolone.

Uses

Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions^[2] such as asthma,^[3] uveitis, pyoderma gangrenosum, rheumatoid arthritis, ulcerative colitis, pericarditis, temporal arteritis and Crohn's disease, Bell's palsy, multiple sclerosis,^[4] cluster headaches, vasculitis, acute lymphoblastic leukemia and autoimmune hepatitis,^[5] systemic lupus erythematosus, Kawasaki disease^[6] and dermatomyositis. It is also used for treatment of sarcoidosis, though the mechanism is unknown.

Prednisolone acetate ophthalmic suspension (eye drops) is an adrenocortical steroid product, prepared as a sterile ophthalmic suspension and used to reduce swelling, redness, itching, and allergic reactions affecting the eye.

Prednisolone can also be used as an immunosuppressive drug for organ transplants and in cases of primary adrenal insufficiency (Addison's disease).

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and, it is presumed, delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation with inflammation.

Mechanism of action

Prednisolone irreversibly binds with glucocorticoid receptors (GR) alpha and beta for which they have a high affinity. AlphaGR and BetaGR are found in virtually all tissues with variable numbers between 3000 and 10000 per cell, depending on the tissue involved. Prednisolone can activate and influence biochemical behaviour of most cells. The steroid/receptor complexes dimerise and interact with cellular DNA in the nucleus, binding to steroid-response elements and modifying gene transcription. They induce synthesis of some proteins, and inhibit synthesis of others.^[7]^[8]

Not all metabolic actions on genes are known. Most mediator proteins are enzymes, e.g., cAMP-dependent kinase

Anti-inflammatory and immunosuppressive actions:

Inhibition of gene transcription for COX-2, cytokines, cell adhesion molecules, and inducible NO synthase
Blockage of Vitamin D3-mediated induction of osteocalcin gene in osteoblasts
Modification of collegenase gene transcription
Increase synthesis annexin-1, important in negative feedback on hypothalamus and anterior pituitary gland

Regulation of gene suppression leads to systemic suppression of inflammation and immune response. This is of clinical usefulness but ultimately leads to gluconeogenesis, proteolysis and lipolysis. Gene transcription returns to normal after cessation, but sudden stoppage can cause Addison's disease. Osteoporosis is permanent.

Adverse effects

Possible side-effects include fluid retention of the face (moon face, Cushing's syndrome), acne, constipation, and mood swings.

A lengthy course of prednisolone can cause bloody or black tarry stools from bleeding into the stomach (this requires urgent medical attention); filling or rounding out of the face; muscle cramps or pain; muscle weakness; nausea; pain in back, hips, ribs, arms, shoulders, or legs; reddish-purple stretch marks on arms, face, legs, trunk, or groin; thin and shiny skin; unusual bruising; urinating at night; rapid weight gain; and wounds that will not heal.

Prolonged use of prednisolone can lead to the development of osteoporosis which makes bones more fragile and susceptible to fractures. One way to help alleviate this side effect is through the use of calcium and vitamin D supplements.^[9]

Swelling of the pancreas has also been reported.^[10]

Prednisolone can cause increased blood sugar levels for diabetics.

Other effects include decreased or blurred vision, increased eye pressure, increased thirst, cataract formation, confusion, rare cases of dementia in otherwise-healthy elderly patients, and nervousness.

Loteprednol is an analog drug that has reduced adverse ocular effects.

Prednisolone may cause serious mental health problems, these affect around 5% who take such steroids.^[10] Symptoms include:

depression, including suicidal thoughts
feeling high (mania) or mood swings
anxiety
insomnia
difficulty in thinking / confusion
memory loss
visual, auditory or tactile hallucinations
having strange and frightening thoughts, changing behaviour or having feelings of being alone

Nasal septum perforation and bowel perforation are also notable adverse effects that restrict steroids' use in some pathologic conditions.^[11]^[12]

Withdrawal from prednisolone can be problematic after taking large doses or over more than two weeks.^[13] This is caused by prednisolone inhibiting the natural production of corticosteroids in the "Hypothalamic-Pituitary-Adrenal Axis" (HPAA)^[13]

Banned status in athletics

As a glucocorticosteroid, unauthorized or ad-hoc use of prednisolone during competition via oral, intravenous, intramuscular or rectal routes is banned under WADA anti-doping rules.^[14] The drug may be used in competition with a TUE (Therapeutic Use Exemption), in compliance with WADA regulations. Local or topical use of prednisolone during competition as well as any use out of competition is not regulated.

References

^ Davis M, Williams R, Chakraborty J et al. (June 1978). "Prednisone or prednisolone for the treatment of chronic active hepatitis? A comparison of plasma availability". British Journal of Clinical Pharmacology 5 (6): 501–5. doi:10.1111/j.1365-2125.1978.tb01664.x. PMC 1429358. PMID 656293.
^ Czock D, Keller F, Rasche FM, Häussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. Review. PMID 15634032
^ Fiel SB, Vincken W. Systemic corticosteroid therapy for acute asthma exacerbations. J Asthma. 2006 Jun-Jul;43(5):321-31. Review. PMID 16801135
^ Thrower BW. Relapse management in multiple sclerosis. Neurologist. 2009 Jan;15(1):1-5. Review. PMID 19131851
^ Lambrou GI, Vlahopoulos S, Papathanasiou C, Papanikolaou M, Karpusas M, Zoumakis E, Tzortzatou-Stathopoulou F. Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression. Leuk Res. 2009 May 16. [Epub ahead of print] PMID 19450877
^ Miura M, Tamame T, Naganuma T, Chinen S, Matsuoka M, & Ohki H. (2011). Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy. Paediatrics & Child Health. 16(8), 479-84. PMID 23024586
^ Prednisolone. Australian Medicines Handbook 2010. Adelaide: Australian Medicines handbook Pty Ltd.; 2010. 497, 598.
^ Rang HP, Dale MM, Ritter JM, Moore PK. The pituitary and the adrenal Cortex. Hunter l, editor. Pharmacology. 5th ed. London: Churchill Livingstone; 2003. 413, 415.
^ "prednisolone, Pediapred Oral Liquid, Medrol (cont.)".
^ ^a ^b Drugs Information. "Prednisolone Tablets 1mg, 5mg (Actavis UK Ltd)". Retrieved 13 December 2012.
^ "Bowel Perforation in Steroid-Treated Patients"
^ "Intranasal steroids and septum perforation--an overlooked complication?"
^ ^a ^b Kaminstein, David. "Steroid Withdrawal". medicinenet. Retrieved 23 December 2012.
^ "The 2011 Prohibited List".

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English Journal

Ocular pharmacokinetics of mapracorat, a novel, selective glucocorticoid receptor agonist, in rabbits and monkeys.

Proksch JW, Lowe ER, Ward KW.SourceDrug Metabolism and Pharmacokinetics, Bausch & Lomb, Inc., 1400 N. Goodman St., Rochester, NY 14609. joel_w_proksch@bausch.com.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2011 Jul;39(7):1181-7. Epub 2011 Mar 25.
Mapracorat is a selective glucocorticoid receptor agonist in development for the treatment of a variety of ocular diseases. The purpose of this investigation was to evaluate the ocular pharmacokinetics of mapracorat after topical dosing over a range of dose levels in rabbits and monkeys. Mapracorat
PMID 21441467

Japanese Journal

Eosinophilic Enteritis: Efficiency of the 13C-Acetate Breath Test for Assessing the Disease Activity

Yoda Aya,Takeshima Fuminao,Kadota Koichiro,Inoue Keita,Nakamichi Seiko,Hayashi Tomayoshi,Nakao Kazuhiko,Oozono Yoshiyuki
Internal Medicine 51(18), 2551-2554, 2012
… The patient received oral prednisolone and his symptoms improved. … Both at the onset and at relapse of the disease, the maximal 13CO2 excretion time (Tmax) of 13C-acetate breath test was noted to have increased levels of excretion. … This is the first report of a case of eosinophilic enteritis in which the 13C-acetate breath test was effective for assessing the disease activity and evaluating the effectiveness of treatment. …
NAID 130002062395

臨床経験脊柱管狭窄症に高比重ブピヴァカインと酢酸メチルプレドニゾロンのクモ膜下腔への注入効果

緒方博丸
東洋医学とペインクリニック 40(1・2), 2-7, 2010-08
NAID 40017328967

Successful treatment of obstructive jaundice by administration of prifinium bromide and ursodeoxycholic acid in a Japanese Black cow

松雪暁子,渡辺大作,岩崎梢,佐藤健太郎,大塚浩通,畑井仁,及川正明
Japanese Journal of Large Animal Clinics 1(1), 19-24, 2010
… Therefore, we treated by intravenous (i.v.) injection of acetate Ringers and 5 % glucose solution with added ursodeoxycholic acid (UDCA, 473.5 mg/day), and intramuscular (i.m.) injection of prednisolone (PDL, 100 mg/day). …
NAID 130003358457

「prednisolone sodium succinate」

Prednisolone
Systematic (IUPAC) name
	(11β)-11,17,21-trihydroxypregna-1,4-diene-3,20-dione
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682794
Licence data	US FDA:link
Pregnancy; category	AU: A; US: C (Risk not ruled out);
Legal status	UK: Prescription-only (POM); US: ℞-only;
Pharmacokinetic data
Half-life	2-3 hours
Excretion	Prednisolone is excreted via urine
Identifiers
CAS Registry Number	50-24-8
ATC code	A07EA01 C05AA04, D07AA03, H02AB06, R01AD02, S01BA04, S02BA03, S03BA02
PubChem	CID: 5755
IUPHAR ligand	2866
DrugBank	DB00860
ChemSpider	5552
UNII	9PHQ9Y1OLM
KEGG	D00472
ChEBI	CHEBI:8378
ChEMBL	CHEMBL131
Synonyms	11,17-dihydroxy-17- (2-hydroxyacetyl)- 10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17- dodecahydrocyclopenta [a]phenanthren-3-one
Chemical data
Formula	C21H28O5
Molecular mass	360.444 g/mol
	SMILES O=C\1\C=C/[C@]4(/C(=C/1)CC[C@@H]2[C@@H]4[C@@H](O)C[C@@]3([C@@](O)(C(=O)CO)CC[C@@H]23)C)C;
	InChI InChI=1S/C21H28O5/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/h5,7,9,14-16,18,22,24,26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1 ; Key:OIGNJSKKLXVSLS-VWUMJDOOSA-N ;
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