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{{Short description|Glucocorticoid and Mineralocorticoid hormone Cortisol supplied as a medication}} {{Use dmy dates|date=August 2021}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464366483 | image = Cortisol3.svg | image_class = skin-invert-image | width = 225 | alt = | image2 = Cortisol-3D-balls.png | alt2 = <!--Clinical data --> | Drugs.com = {{drugs.com|monograph|hydrocortisone}} | tradename = Cortef, others<ref name=AHFS2016/> | MedlinePlus = a682206 | DailyMedID = Hydrocortisone | pregnancy_AU = A | pregnancy_AU_comment = <ref>{{cite web | title=Prescribing medicines in pregnancy database | website=[[Therapeutic Goods Administration]] (TGA) | url=https://www.tga.gov.au/prescribing-medicines-pregnancy-database | access-date=21 February 2021 | archive-date=20 December 2016 | archive-url=https://web.archive.org/web/20161220210434/https://www.tga.gov.au/prescribing-medicines-pregnancy-database | url-status=live }}</ref> | class = [[Glucocorticoid]]; [[Mineralocorticoid]] | routes_of_administration = [[Oral administration|By mouth]], [[intravenous administration|intravenous]], [[topical medication|topical]], [[rectal administration|rectal]] | ATC_prefix = A01 | ATC_suffix = AC03 | ATC_supplemental = {{ATC|A07|EA02}}, {{ATC|C05|AA01}}, {{ATC|D07|AA02}}, {{ATC|D07|XA01}}, {{ATC|H02|AB09}}, {{ATC|S01|BA02}}, {{ATC|S01|CB03}}, {{ATC|S02|BA01}} <!-- Legal status --> | legal_AU = S4 | legal_AU_comment = / S3 / S2 | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> | legal_BR_comment = | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = / P / GSL | legal_US = OTC | legal_US_comment = / Rx-only<ref>{{cite web |url=https://s3.amazonaws.com/archives.federalregister.gov/issue_slice/1991/8/30/43023-43026.pdf#page=3 |title=Hydrocortisone Notice of enforcement policy |publisher=FDA |format=PDF |access-date=31 December 2022 |archive-date=12 March 2023 |archive-url=https://web.archive.org/web/20230312130747/https://s3.amazonaws.com/archives.federalregister.gov/issue_slice/1991/8/30/43023-43026.pdf#page=3 |url-status=live }}</ref><ref>{{cite web | title=Ala-cort- hydrocortisone cream | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de000081-a245-4f6b-9e7c-e47d84b82338 | access-date=21 February 2021 | archive-date=27 October 2020 | archive-url=https://web.archive.org/web/20201027063841/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de000081-a245-4f6b-9e7c-e47d84b82338 | url-status=live }}</ref><ref>{{cite web | title=Ala-scalp- hydrocortisone lotion | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ecba1d44-33a9-44d7-ad06-13ada2375c72 | access-date=21 February 2021 | archive-date=21 April 2021 | archive-url=https://web.archive.org/web/20210421014247/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ecba1d44-33a9-44d7-ad06-13ada2375c72 | url-status=live }}</ref><ref>{{cite web | title=Alkindi Sprinkle- hydrocortisone granule | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682 | access-date=21 February 2021 | archive-date=10 February 2022 | archive-url=https://web.archive.org/web/20220210170834/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682 | url-status=live }}</ref><ref name="anusol-acetate">{{cite web | title=Anusol HC- hydrocortisone acetate suppository | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a562f3d7-2692-4357-aade-ae50afcbfddd | access-date=21 February 2021 | archive-date=10 February 2022 | archive-url=https://web.archive.org/web/20220210170835/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a562f3d7-2692-4357-aade-ae50afcbfddd | url-status=live }}</ref><ref>{{cite web | title=Cortef- hydrocortisone tablet | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9ce19944-dd88-4a7b-84ca-b07f4ec23bad | access-date=21 February 2021 | archive-date=17 April 2021 | archive-url=https://web.archive.org/web/20210417030800/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9ce19944-dd88-4a7b-84ca-b07f4ec23bad | url-status=live }}</ref> | legal_EU = OTC | legal_EU_comment = / Rx-only<ref name="Efmody EPAR" /><ref>{{cite web | title=Efmody Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1549.htm | access-date=3 March 2023 | archive-date=5 March 2023 | archive-url=https://web.archive.org/web/20230305042206/https://ec.europa.eu/health/documents/community-register/html/h1549.htm | url-status=live }}</ref> | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above --> <!-- Pharmacokinetic data --> | bioavailability = [[Oral administration|Oral]]: 96 ± 20%<ref name="pmid15634032" /><ref name="pmid18611115" /> | protein_bound = 92 ± 2% (92–93%)<ref name="pmid15634032" /><ref name="pmid18611115" /> | metabolism = {{Abbrlink|11β-HSDs|11β-Hydroxysteroid dehydrogenases}}, others<ref name="pmid18611115" /> | metabolites = [[Cortisone]], others<ref name="pmid18611115" /> | onset = Oral: 1.2 ± 0.4 hours ([[Tmax (pharmacology)|T<sub>max</sub>]])<ref name="pmid15634032" /> | elimination_half-life = 1.2–2.0 hours<ref name="pmid15634032">{{cite journal | vauthors = Czock D, Keller F, Rasche FM, Häussler U | title = Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids | journal = Clinical Pharmacokinetics | volume = 44 | issue = 1 | pages = 61–98 | date = 2005 | pmid = 15634032 | doi = 10.2165/00003088-200544010-00003 | s2cid = 24458998 }}</ref><ref name="pmid18611115">{{cite journal | vauthors = Lennernäs H, Skrtic S, Johannsson G | title = Replacement therapy of oral hydrocortisone in adrenal insufficiency: the influence of gastrointestinal factors | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 4 | issue = 6 | pages = 749–758 | date = June 2008 | pmid = 18611115 | doi = 10.1517/17425255.4.6.749 | s2cid = 73248541 }}</ref> | duration_of_action = 8–12 hours<ref name="pmid23947590" /> | excretion = <!--Identifiers --> | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 50-23-7 | PubChem = 5754 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00741 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 5551 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = WI4X0X7BPJ | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00088 | KEGG2_Ref = {{keggcite|correct|kegg}} | KEGG2 = D00165 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 17650 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 389621 | synonyms = Cortisol; 11β,17α,21-Trihydroxypregn-4-ene-3,20-dione; 11β,17α,21-Trihydroxyprogesterone <!--Chemical data --> | IUPAC_name = (8''S'',9''S'',10''R'',11''S'',13''S'',14''S'',17''R'')-11,17-Dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1''H''-cyclopenta[''a'']phenanthren-3-one | C = 21 | H = 30 | O = 5 | SMILES = O=C4\C=C2/[C@]([C@H]1[C@@H](O)C[C@@]3([C@@](O)(C(=O)CO)CC[C@H]3[C@@H]1CC2)C)(C)CC4 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C21H30O5/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/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = JYGXADMDTFJGBT-VWUMJDOOSA-N }} <!-- Definition and medical uses --> '''Hydrocortisone''' is the name for the hormone [[cortisol]] when supplied as a medication.<ref>{{cite book | vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism|date=2001|publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-1750-2 |page=762 |url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA762|language=en|url-status=live|archive-url=https://web.archive.org/web/20160914013845/https://books.google.ca/books?id=FVfzRvaucq8C&pg=PA762|archive-date=14 September 2016}}</ref> It is a [[corticosteroid]] and works as an [[anti-inflammatory]] and by [[immunosuppressant|immune suppression]].<ref name="AHFS2016" /> Uses include conditions such as [[adrenocortical insufficiency]], [[adrenogenital syndrome]], [[hypercalcemia|high blood calcium]], [[thyroiditis]], [[rheumatoid arthritis]], [[dermatitis]], [[asthma]], and [[COPD]].<ref name="AHFS2016">{{cite web|title=Hydrocortisone|url=https://www.drugs.com/monograph/hydrocortisone.html|website=Drugs.com|publisher=American Society of Health-System Pharmacists|access-date=30 August 2016|date=9 February 2015|url-status=live|archive-url=https://web.archive.org/web/20160920063137/https://www.drugs.com/monograph/hydrocortisone.html|archive-date=20 September 2016}}</ref> It is the treatment of choice for adrenocortical insufficiency.<ref name="Ric2015">{{cite book | vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=978-1-284-05756-0|page=202}}</ref> It can be given [[by mouth]], [[topically]], or by [[Injection (medicine)|injection]].<ref name="AHFS2016" /> Stopping treatment after long-term use should be done slowly.<ref name="AHFS2016" /> <!-- Side effects and mechanism --> Side effects may include mood changes, increased risk of [[infection]], and [[edema]] (swelling).<ref name="AHFS2016" /> With long-term use, common side effects include [[osteoporosis]], [[upset stomach]], [[physical weakness]], easy [[bruising]], and [[candidiasis]] (yeast infections).<ref name="AHFS2016" /> It is unclear if it is safe for use during [[pregnancy]].<ref>{{cite web|title=Hydrocortisone Pregnancy and Breastfeeding Warnings|url=https://www.drugs.com/pregnancy/hydrocortisone.html|website=Drugs.com|access-date=1 September 2016|url-status=live|archive-url=https://web.archive.org/web/20160920090158/https://www.drugs.com/pregnancy/hydrocortisone.html|archive-date=20 September 2016}}</ref> <!-- History and society --> Hydrocortisone was patented in 1936 and approved for medical use in 1941.<ref>{{US patent|2183589}}</ref><ref name=Fis2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=484 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA484 |language=en |access-date=7 September 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110032528/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA484 |url-status=live }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2016/> In 2022, it was the 202nd most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref name="Top 300 of 2022">{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Hydrocortisone Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Hydrocortisone | access-date = 30 August 2024 }}</ref> ==Medical uses== Hydrocortisone is the pharmaceutical term for cortisol used in [[oral administration]], [[intravenous injection]], or [[topical application]]. It is used as an [[immunosuppressive drug]], given by [[Injection (medicine)|injection]] in the treatment of severe [[allergic reactions]] such as [[anaphylaxis]] and [[angioedema]], in place of [[prednisolone]] in patients needing steroid treatment but unable to take oral medication, and perioperatively in patients on long-term steroid treatment to prevent an [[adrenal crisis]]. It may also be injected into inflamed joints resulting from diseases such as [[gout]].{{cn|date=November 2024}} It may be used topically for allergic [[rash]]es, [[eczema]], [[psoriasis]], [[itching]], and other [[Inflammation|inflammatory]] skin conditions. [[Topical hydrocortisone]] creams and ointments are available in most countries without prescription in strengths ranging from 0.05% to 2.5% (depending on local regulations) with stronger forms available by prescription only.{{Citation needed|date=November 2023}} It may also be used rectally in suppositories to relieve the [[Edema|swelling]], [[itch]], and [[irritation]] in [[haemorrhoids|hemorrhoids]].<ref name="anusol-acetate"/> It may be used as an acetate form ([[hydrocortisone acetate]]), which has slightly different pharmacokinetics and pharmacodynamics.<ref name="anusol-acetate"/><ref name="pmid18345402">{{cite journal |vauthors=Leite FM, Longui CA, Kochi C, Faria CD, Borghi M, Calliari LE, Monte O |title=[Comparative study of prednisolone versus hydrocortisone acetate for treatment of patients with the classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency] |language=Portuguese |journal=Arq Bras Endocrinol Metabol |volume=52 |issue=1 |pages=101–8 |date=February 2008 |pmid=18345402 |doi=10.1590/s0004-27302008000100014|doi-access=free }}</ref> <gallery> File:Cortisol for injection.jpg|Cortisol for injection File:Tube of hydrocortisone cream.jpg|A tube of hydrocortisone cream, purchased [[over the counter|over-the-counter]] File:Hydrocortisone Cortef 10 mg Кортеф Гидрокортизон.jpg|Hydrocortisone 10 mg oral tablets (depicted a package for Russian market) </gallery> ==Pharmacology== ===Pharmacodynamics=== Hydrocortisone is a [[corticosteroid]], acting specifically as both a [[glucocorticoid]] and as a [[mineralocorticoid]]. That is, it is an [[agonist]] of the [[glucocorticoid receptor|glucocorticoid]] and [[mineralocorticoid receptor]]s.{{cn|date=November 2024}} Hydrocortisone has low [[potency (pharmacology)|potency]] relative to [[synthetic compound|synthetic]] corticosteroids.<ref name="pmid23947590">{{cite journal | vauthors = Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, Brown JP, Cohen A, Kim H | title = A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy | journal = Allergy Asthma Clin Immunol | volume = 9 | issue = 1 | pages = 30 | date = August 2013 | pmid = 23947590 | pmc = 3765115 | doi = 10.1186/1710-1492-9-30 | doi-access = free | url = }}</ref> Compared to hydrocortisone, [[prednisolone]] is about 4{{nbsp}}times as [[potency (pharmacology)|potent]] and [[dexamethasone]] about 40{{nbsp}}times as potent in terms of [[anti-inflammatory]] effect.<ref name=Dexamethasone>{{cite web|title=Dexamethasone|url=https://www.drugs.com/pro/dexamethasone.html|publisher=drugs.com|access-date=14 June 2013|url-status=live|archive-url=https://web.archive.org/web/20130621041355/http://www.drugs.com/pro/dexamethasone.html|archive-date=21 June 2013}}</ref> Prednisolone can also be used as cortisol replacement, and at replacement dose levels (rather than anti-inflammatory levels), prednisolone is about 8{{nbsp}}times more potent than cortisol.<ref>{{cite journal | vauthors = Caldato MC, Fernandes VT, Kater CE | title = One-year clinical evaluation of single morning dose prednisolone therapy for 21-hydroxylase deficiency | journal = Arquivos Brasileiros de Endocrinologia e Metabologia | volume = 48 | issue = 5 | pages = 705–712 | date = October 2004 | pmid = 15761542 | doi = 10.1590/S0004-27302004000500017 | doi-access = free | s2cid = 13986916 }}</ref> The equivalent doses and relative potencies of hydrocortisone compared to various other synthetic corticosteroids have also been reviewed and summarized.<ref name="pmid23947590" /> The [[endogenous]] [[production rate]] of cortisol is approximately 5.7 to 9.9{{nbsp}}mg/m<sup>2</sup> per day, which corresponds to an oral hydrocortisone dose of approximately 15 to 20{{nbsp}}mg/day (for a 70-kg person).<ref name="Arvat Falorni 2016 p. 1-PA61">{{cite book | vauthors=Arvat E, Falorni A | title=Cortisol Excess and Insufficiency | publisher=S. Karger AG | series=Frontiers of Hormone Research | year=2016 | isbn=978-3-318-05840-6 | url=https://books.google.com/books?id=jew6DAAAQBAJ&pg=RA1-PA61 | access-date=10 April 2023 | page=1-PA61 | archive-date=27 April 2023 | archive-url=https://web.archive.org/web/20230427010953/https://books.google.com/books?id=jew6DAAAQBAJ&pg=RA1-PA61 | url-status=live }}</ref><ref name="GhizzoniCappaChrousos2011">{{cite book | veditors = Ghizzoni L, Cappa M, Chrousos GP, Loche S, Maghnie M | date = 2011 | title = Pediatric Adrenal Diseases: Workshop, May 16-18, 2010, Turin (Italy) | publisher = Karger Medical and Scientific Publishers | pages = 174– | isbn = 978-3-8055-9643-5 | oclc = 1020003143 | url = https://books.google.com/books?id=gde44-zDr_oC&pg=PA174 | access-date = 10 April 2023 | archive-date = 10 April 2023 | archive-url = https://web.archive.org/web/20230410220229/https://books.google.com/books?id=gde44-zDr_oC&pg=PA174 | url-status = live }}</ref> One review described daily cortisol production of 10{{nbsp}}mg in healthy volunteers and reported that daily cortisol production could increase up to 400{{nbsp}}mg in conditions of severe [[stress (biology)|stress]] (e.g., [[surgery]]).<ref name="pmid15634032" /> The total and/or free concentrations of cortisol/hydrocortisone required for various glucocorticoid effects have been determined.<ref name="pmid15634032" /> ===Pharmacokinetics=== ====Absorption==== The [[bioavailability]] of [[oral administration|oral]] hydrocortisone is about 96% ± 20% ([[Standard Deviation|SD]]).<ref name="pmid15634032" /><ref name="pmid18611115" /> The pharmacokinetics of hydrocortisone are non-linear.<ref name="pmid15634032" /> The [[Cmax (pharmacology)|peak level]] of oral hydrocortisone is 15.3 ± 2.9 (SD) μg/L per 1{{nbsp}}mg dose.<ref name="pmid15634032" /> The [[Tmax (pharmacology)|time to peak concentrations]] of oral hydrocortisone is 1.2 ± 0.4 (SD) hours.<ref name="pmid15634032" /> The [[topical administration|topical]] [[percutaneous]] [[absorption (pharmacokinetics)|absorption]] of hydrocortisone varies widely depending on experimental circumstances and has been reported to range from 0.5 to 14.9% in different studies.<ref name="pmid8299376">{{cite journal | vauthors = Wester RC, Maibach HI | title = Percutaneous absorption of topical corticosteroids | journal = Current Problems in Dermatology | volume = 21 | issue = | pages = 45–60 | date = 1993 | pmid = 8299376 | doi = 10.1159/000422362 | isbn = 978-3-8055-5712-2 }}</ref> Some skin application sites, like the [[scrotum]] and [[vulva]], absorb hydrocortisone much more efficiently than other application sites, like the [[forearm]].<ref name="pmid8299376" /><ref name="pmid32643443">{{cite journal | vauthors = Bormann JL, Maibach HI | title = Effects of anatomical location on ''in vivo'' percutaneous penetration in man | journal = Cutaneous and Ocular Toxicology | volume = 39 | issue = 3 | pages = 213–222 | date = September 2020 | pmid = 32643443 | doi = 10.1080/15569527.2020.1787434 | s2cid = 220439810 }}</ref><ref name="WesterMaibach2021">{{cite book | title = Percutaneous Absorption | vauthors = Wester RC, Maibach HI | chapter = Regional Variation in Percutaneous Absorption | date = 8 June 2021 | pages = 165–174 | publisher = CRC Press | doi = 10.1201/9780429202971-11 | isbn = 978-0-429-20297-1 | s2cid = 132864025 | url = }}</ref> In one study, the amount of hydrocortisone absorbed ranged from 0.2% to 36.2% depending on the application site, with the ball of the foot having the lowest absorption and the scrotum having the highest absorption.<ref name="WesterMaibach2021" /> The absorption of hydrocortisone by the vulva has ranged from 4.4 to 8.1%, relative to 1.3 to 2.8% for the arm, in different studies and subjects.<ref name="WesterMaibach2021" /><ref name="pmid7406539">{{cite journal | vauthors = Britz MB, Maibach HI, Anjo DM | title = Human percutaneous penetration of hydrocortisone: the vulva | journal = Archives of Dermatological Research | volume = 267 | issue = 3 | pages = 313–316 | date = 1980 | pmid = 7406539 | doi = 10.1007/BF00403852 | s2cid = 33367289 }}</ref><ref name="pmid8746334">{{cite journal | vauthors = Oriba HA, Bucks DA, Maibach HI | title = Percutaneous absorption of hydrocortisone and testosterone on the vulva and forearm: effect of the menopause and site | journal = The British Journal of Dermatology | volume = 134 | issue = 2 | pages = 229–233 | date = February 1996 | pmid = 8746334 | doi = 10.1111/j.1365-2133.1996.tb07606.x | s2cid = 30076779 }}</ref> ====Distribution==== Most cortisol in the blood (all but about 4%) is [[plasma protein binding|bound to proteins]], including [[transcortin|corticosteroid binding globulin]] (CBG) and [[serum albumin]]. A pharmacokinetic review stated that 92% ± 2% (SD) (92–93%) of hydrocortisone is plasma protein-bound.<ref name="pmid15634032" /> Free cortisol passes easily through cellular membranes.<ref>{{cite journal | vauthors = Charmandari E, Johnston A, Brook CG, Hindmarsh PC | title = Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency | journal = The Journal of Endocrinology | volume = 169 | issue = 1 | pages = 65–70 | date = April 2001 | pmid = 11250647 | doi = 10.1677/joe.0.1690065 | doi-access = free }}</ref> Inside cells it interacts with [[corticosteroid receptor]]s.<ref name="isbn1-4377-1753-5">{{cite book |vauthors=Boron WF, Boulpaep EL | title = Medical Physiology | edition = 2nd | publisher = Saunders | location = Philadelphia | year = 2011 | isbn = 978-1-4377-1753-2 }}</ref> ====Metabolism==== Hydrocortisone is [[metabolism|metabolized]] by [[11β-hydroxysteroid dehydrogenase]]s (11β-HSDs) into [[cortisone]], an inactive [[metabolite]].<ref name="pmid18611115" /><ref name="pmid15634032" /> It is additionally [[5α-reductase|5α-]], [[5β-reductase|5β-]], and [[3α-hydroxysteroid dehydrogenase|3α-reduced]] into [[dihydrocortisol]]s, [[dihydrocortisone]]s, [[tetrahydrocortisol]]s, and [[tetrahydrocortisone]]s.<ref name="pmid33418075">{{cite journal | vauthors = Nikolaou N, Hodson L, Tomlinson JW | title = The role of 5-reduction in physiology and metabolic disease: evidence from cellular, pre-clinical and human studies | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 207 | issue = | pages = 105808 | date = March 2021 | pmid = 33418075 | doi = 10.1016/j.jsbmb.2021.105808 | s2cid = 230716310 }}</ref><ref name="pmid15634032" /><ref name="pmid18611115" /> ====Elimination==== The [[elimination half-life]] of hydrocortisone ranges from about 1.2 to 2.0 (SD) hours, with an average of around 1.5{{nbsp}}hours, regardless of [[oral administration|oral]] versus [[parenteral administration]].<ref name="pmid15634032" /><ref name="pmid18611115" /> The [[duration of action]] of [[systemic administration|systemic]] hydrocortisone has been listed as 8 to 12{{nbsp}}hours.<ref name="pmid23947590" /> ==Chemistry== {{See also|List of corticosteroids|List of corticosteroid esters#Hydrocortisone esters}} Hydrocortisone, also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione, is a [[natural product|naturally occurring]] [[pregnane]] [[steroid]].<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |url= https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA316|date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=316 |url-status=live |archive-url=https://web.archive.org/web/20170908213347/https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA316|archive-date=8 September 2017}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA524|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=524–|access-date=19 June 2020|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110093813/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA524|url-status=live}}</ref> A variety of [[hydrocortisone ester]]s exist and have been marketed for medical use.<ref name="Elks2014" /><ref name="IndexNominum2000" /> == Society and culture == === Legal status === In March 2021, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Efmody, intended for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older.<ref name="Efmody: Pending EC decision" /> The applicant for this medicinal product is Diurnal Europe BV.<ref name="Efmody: Pending EC decision">{{cite web | title=Efmody: Pending EC decision | website=[[European Medicines Agency]] (EMA) | date=25 March 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/efmody | access-date=27 March 2021 | archive-date=4 May 2021 | archive-url=https://web.archive.org/web/20210504065409/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/efmody | url-status=dead }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Hydrocortisone (Efmody) was approved for medical use in the European Union, in May 2021, for the treatment of [[congenital adrenal hyperplasia]] (CAH) in people aged twelve years and older.<ref name="Efmody EPAR">{{cite web | title=Efmody EPAR | website=[[European Medicines Agency]] (EMA) | date=24 March 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/efmody | access-date=14 June 2021 | archive-date=14 June 2021 | archive-url=https://web.archive.org/web/20210614223631/https://www.ema.europa.eu/en/medicines/human/EPAR/efmody | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> ===Anti-competitive practices=== In the UK, the [[Competition and Markets Authority]] (CMA) concluded an investigation into the supply of hydrocortisone tablets, finding that from October 2008 onwards, drug suppliers Auden McKenzie and [[Actavis plc]] had charged "excessive and unfair prices" for 10mg and 20mg tablets and entered into agreements with potential competitors, paying companies who agreed not to enter the hydrocortisone market and enabling Auden McKenzie and Actavis to supply the drugs as "[[generic drug|generic]]" rather than branded products and thereby escape price controls until eventually other companies entered the market. Auden and Actavis overcharged the UK's [[National Health Service]] for over ten years. Fines totalling over £255m were levied against the companies involved in this breach of [[competition law]].<ref>{{OGL-attribution|Competition and Markets Authority, [https://assets.publishing.service.gov.uk/media/624597bbe90e075f0b5a3da4/Case_50277_Decision.pdf Decision: Hydrocortisone tablets. Excessive and unfair pricing and Anti-competitive agreements], published 31 March 2022, accessed 1 June 2023}}</ref> == Research == ===COVID-19=== Hydrocortisone was found to be effective in reducing mortality rate of critically ill [[COVID-19]] patients when compared to other usual care or a placebo.<ref>{{cite journal | vauthors = Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LC, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JP, Horby P, Jüni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Møller MH, Perner A, Petersen MW, Savovic J, Tomazini B, Veiga VC, Webb S, Marshall JC | title = Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis | journal = JAMA | volume = 324 | issue = 13 | pages = 1330–1341 | date = October 2020 | pmid = 32876694 | pmc = 7489434 | doi = 10.1001/jama.2020.17023 | doi-access = free }}</ref> == References == {{Reflist}} {{Stomatological preparations}} {{Antidiarrheals, intestinal anti-inflammatory and anti-infective agents}} {{Vasoprotectives}} {{Glucocorticoids and antiglucocorticoids}} {{Corticosteroids}} {{Otologicals}} {{Glucocorticoid receptor modulators}} {{Portal bar | Medicine}} {{Authority control}} [[Category:Alcohols]] [[Category:Antipruritics]] [[Category:CYP3A4 inducers]] [[Category:Glucocorticoids]] [[Category:Ketones]] [[Category:Mineralocorticoids]] [[Category:Orphan drugs]] [[Category:Pregnanes]] [[Category:World Health Organization essential medicines]] [[Category:Wikipedia medicine articles ready to translate]]
Hydrocortisone
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