as medoxomil: InChI=1S/C30H24N4O8 /c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26/h4-14H,3,15-16H2,1-2H3,(H,32,33,36)
Like other ARBs, azilsartan has an extended diphenyl group within the structure. An interesting aspect of the molecule is that unlike other ARBs which have a tetrazole attached to the molecule, azilsartan has an oxadiazole, which has an acidic proton at the nitrogen. The tetrazole represents a non-classical bio-isostere. The carboxylate seen in the molecule is the active moiety after the molecule has been metabolized. Azilsartan is a pro-drug.[medical citation needed]
Medical usesedit
Azilsartan is used for the treatment of hypertension in adults.[5][8][2] One of the benefits of the medication is that Azilsartan does not need dose adjustments for patients with renal or hepatic dysfunction.
Contraindicationsedit
Azilsartan must not be used with aliskiren, a renin inhibitor, in patients with diabetes as this increases the risk of serious adverse effects.[5][2] Like other antihypertensive drugs acting on the renin–angiotensin system, it is contraindicated during the second and third trimesters of pregnancy.[5][8][9] It should not be used during pregnancy.[2][10]
Interactionsedit
No relevant drug interactions have been found in studies.[8][9] Based on experiences with other drugs acting on the renin–angiotensin system, it is theorized that azilsartan could increase the toxicity of lithium and of other drugs increasing potassium levels, such as potassium sparing diuretics.[8][9]
Azilsartan medoxomil lowers blood pressure by blocking the action of angiotensin II at the AT1 receptor, a hormone that contracts blood vessels and reduces water excretion through the kidneys.[8]
Pharmacokineticsedit
Azilsartan medoxomil is quickly absorbed from the gut, independently of food intake. Maximal blood plasma concentrations are reached after one to three hours. The liver enzyme CYP2C9 is involved in the formation of the two main metabolites, which are pharmacologically inactive; they are the O-deethylation and decarboxylation products of azilsartan. Elimination half life is about 11 hours. 55% are excreted via the feces, and 42% via the urine, of which 15% are present as azilsartan and the rest in form of the metabolites.[9]
The drug formulation contains the potassium salt of azilsartan medoxomil (codenamed TAK-491), an ester of azilsartan's carboxyl group with the alcohol (5-methyl-2-oxo-1,3-dioxol-4-yl)methanol.[9] This ester is more lipophilic than azilsartan itself.
Historyedit
In February 2011, the U.S. Food and Drug Administration (FDA) approved azilsartan medoxomil for the treatment of high blood pressure in adults.[11][12] In July 2011, azilsartan medoxomil was approved in the European Union for the treatment of essential hypertension.[5] In March 2012, Health Canada approved the drug for mild to moderate essential hypertension.[13]
In December 2014, Valeant Canada acquired the marketing rights to Edarbi and Edarbyclor from Takeda Pharmaceutical.[14]
Referencesedit
^"Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
^ abcde"Edarbi- azilsartan kamedoxomil tablet". DailyMed. 26 July 2019. Retrieved 9 March 2020.
^Pradhan A, Tiwari A, Sethi R (2019). "Azilsartan: Current Evidence and Perspectives in Management of Hypertension". International Journal of Hypertension. 2019: 1824621. doi:10.1155/2019/1824621. PMC6925743. PMID 31885897.
^"2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. from the original on 30 June 2023. Retrieved 30 June 2023.
^"Drug Approval Package:Edarbyclor (azilsartan medoxomil and chlorthalidone) NDA #202331". U.S. Food and Drug Administration (FDA). 16 August 2012. Retrieved 11 March 2020.
^ abcdeDinnendahl V, Fricke U, eds. (2012). Arzneistoff-Profile (in German). Vol. 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN978-3-7741-9846-3.
^"Azilsartan medoxomil (Edarbi) Use During Pregnancy". Drugs.com. 28 February 2020. Retrieved 9 March 2020.
^"Drug Approval Package: Edarbi (azilsartan medoxomil) NDA 200796". U.S. Food and Drug Administration (FDA). 4 April 2011. Retrieved 9 March 2020.
^ (Press release). U.S. Food and Drug Administration. 25 February 2011. Archived from the original on 18 January 2017. Retrieved 1 March 2011.
^"Summary Basis of Decision - Edarbi - Health Canada". Government of Canada. 26 June 2012. Retrieved 6 March 2021.
^"Valeant Canada acquires rights to Edarbi and Edarbyclor for the Canadian market" (Press release). Valeant Canada. 17 December 2014. Retrieved 9 March 2020 – via Cision.
azilsartan, sold, under, brand, name, edarbi, among, others, used, treatment, hypertension, used, prodrug, azilsartan, medoxomil, angiotensin, receptor, antagonist, developed, takeda, clinical, datatrade, namesedarbi, azilvaother, namestak, 491ahfs, drugs, com. Azilsartan sold under the brand name Edarbi among others is used for the treatment of hypertension 2 3 4 It is used as the prodrug azilsartan medoxomil is an angiotensin II receptor antagonist 5 and was developed by Takeda AzilsartanClinical dataTrade namesEdarbi AzilvaOther namesTAK 536 TAK 491AHFS Drugs comMonographMedlinePlusa611028License dataUS DailyMed AzilsartanRoutes ofadministrationBy mouthATC codeC09CA09 WHO C09DA09 WHO Legal statusLegal statusCA only 1 UK POM Prescription only US only EU Rx only In general Prescription only Pharmacokinetic dataBioavailability60 MetabolismCYP2C9Elimination half life11 hrsExcretion55 feces 42 urineIdentifiersIUPAC name 2 Ethoxy 1 2 5 oxo 2 5 dihydro 1 2 4 oxadiazol 3 yl 4 biphenylyl methyl 1H benzimidazole 7 carboxylic acidCAS Number147403 03 0 Yas medoxomil 863031 21 4 YPubChem CID135415867as medoxomil 135409642IUPHAR BPS6901DrugBankas medoxomil DB08822 NChemSpider8001032 Nas medoxomil 9413866 NUNIIF9NUX55P23as medoxomil LL0G25K7I2 YKEGGD08864 Nas medoxomil D08067 NChEBICHEBI 68850 Nas medoxomil CHEBI 68845 NChEMBLChEMBL57242 Nas medoxomil ChEMBL2028661 NCompTox Dashboard EPA DTXSID70163712ECHA InfoCard100 235 975Chemical and physical dataFormulaC 25H 20N 4O 5Molar mass456 458 g mol 13D model JSmol Interactive imageSMILES CCOC1 NC2 CC CC C2N1CC3 CC C C C3 C4 CC CC C4C5 NOC O N5 C O OInChI InChI InChI 1S C25H20N4O5 c1 2 33 24 26 20 9 5 8 19 23 30 31 21 20 29 24 14 15 10 12 16 13 11 15 17 6 3 4 7 18 17 22 27 25 32 34 28 22 h3 13H 2 14H2 1H3 H 30 31 H 27 28 32 NKey KGSXMPPBFPAXLY UHFFFAOYSA N Nas medoxomil InChI 1S C30H24N4O8 c1 3 38 28 31 23 10 6 9 22 27 35 39 16 24 17 2 40 30 37 41 24 25 23 34 28 15 18 11 13 19 14 12 18 20 7 4 5 8 21 20 26 32 29 36 42 33 26 h4 14H 3 15 16H2 1 2H3 H 32 33 36 Key QJFSABGVXDWMIW UHFFFAOYSA N N Y what is this verify The most common adverse reaction in adults is diarrhea 2 It is available as a generic medication 6 It is also sold as a combination drug with chlortalidone under the brand name Edarbyclor 7 Contents 1 Structure activity relationship 2 Medical uses 3 Contraindications 4 Interactions 5 Pharmacology 5 1 Mechanism of action 5 2 Pharmacokinetics 6 Chemistry 7 History 8 ReferencesStructure activity relationship editLike other ARBs azilsartan has an extended diphenyl group within the structure An interesting aspect of the molecule is that unlike other ARBs which have a tetrazole attached to the molecule azilsartan has an oxadiazole which has an acidic proton at the nitrogen The tetrazole represents a non classical bio isostere The carboxylate seen in the molecule is the active moiety after the molecule has been metabolized Azilsartan is a pro drug medical citation needed Medical uses editAzilsartan is used for the treatment of hypertension in adults 5 8 2 One of the benefits of the medication is that Azilsartan does not need dose adjustments for patients with renal or hepatic dysfunction Contraindications editAzilsartan must not be used with aliskiren a renin inhibitor in patients with diabetes as this increases the risk of serious adverse effects 5 2 Like other antihypertensive drugs acting on the renin angiotensin system it is contraindicated during the second and third trimesters of pregnancy 5 8 9 It should not be used during pregnancy 2 10 Interactions editNo relevant drug interactions have been found in studies 8 9 Based on experiences with other drugs acting on the renin angiotensin system it is theorized that azilsartan could increase the toxicity of lithium and of other drugs increasing potassium levels such as potassium sparing diuretics 8 9 Pharmacology editMechanism of action edit Main article Angiotensin II receptor antagonist Azilsartan medoxomil lowers blood pressure by blocking the action of angiotensin II at the AT1 receptor a hormone that contracts blood vessels and reduces water excretion through the kidneys 8 Pharmacokinetics edit Azilsartan medoxomil is quickly absorbed from the gut independently of food intake Maximal blood plasma concentrations are reached after one to three hours The liver enzyme CYP2C9 is involved in the formation of the two main metabolites which are pharmacologically inactive they are the O deethylation and decarboxylation products of azilsartan Elimination half life is about 11 hours 55 are excreted via the feces and 42 via the urine of which 15 are present as azilsartan and the rest in form of the metabolites 9 Chemistry edit nbsp Azilsartan medoxomil the prodrug The drug formulation contains the potassium salt of azilsartan medoxomil codenamed TAK 491 an ester of azilsartan s carboxyl group with the alcohol 5 methyl 2 oxo 1 3 dioxol 4 yl methanol 9 This ester is more lipophilic than azilsartan itself History editIn February 2011 the U S Food and Drug Administration FDA approved azilsartan medoxomil for the treatment of high blood pressure in adults 11 12 In July 2011 azilsartan medoxomil was approved in the European Union for the treatment of essential hypertension 5 In March 2012 Health Canada approved the drug for mild to moderate essential hypertension 13 In December 2014 Valeant Canada acquired the marketing rights to Edarbi and Edarbyclor from Takeda Pharmaceutical 14 References edit Product monograph brand safety updates Health Canada February 2024 Retrieved 24 March 2024 a b c d e Edarbi azilsartan kamedoxomil tablet DailyMed 26 July 2019 Retrieved 9 March 2020 Hardin MD Jacobs TF July 2021 Azilsartan StatPearls Internet Treasure Island FL StatPearls Publishing PMID 30860708 Pradhan A Tiwari A Sethi R 2019 Azilsartan Current Evidence and Perspectives in Management of Hypertension International Journal of Hypertension 2019 1824621 doi 10 1155 2019 1824621 PMC 6925743 PMID 31885897 a b c d e Edarbi EPAR European Medicines Agency EMA 18 May 2018 Retrieved 9 March 2020 2022 First Generic Drug Approvals U S Food and Drug Administration FDA 3 March 2023 Archived from the original on 30 June 2023 Retrieved 30 June 2023 Drug Approval Package Edarbyclor azilsartan medoxomil and chlorthalidone NDA 202331 U S Food and Drug Administration FDA 16 August 2012 Retrieved 11 March 2020 a b c d e Haberfeld H ed 2015 Austria Codex in German Vienna Osterreichischer Apothekerverlag Edarbi Tabletten a b c d e Dinnendahl V Fricke U eds 2012 Arzneistoff Profile in German Vol 2 26 ed Eschborn Germany Govi Pharmazeutischer Verlag ISBN 978 3 7741 9846 3 Azilsartan medoxomil Edarbi Use During Pregnancy Drugs com 28 February 2020 Retrieved 9 March 2020 Drug Approval Package Edarbi azilsartan medoxomil NDA 200796 U S Food and Drug Administration FDA 4 April 2011 Retrieved 9 March 2020 FDA approves Edarbi to treat high blood pressure Press release U S Food and Drug Administration 25 February 2011 Archived from the original on 18 January 2017 Retrieved 1 March 2011 Summary Basis of Decision Edarbi Health Canada Government of Canada 26 June 2012 Retrieved 6 March 2021 Valeant Canada acquires rights to Edarbi and Edarbyclor for the Canadian market Press release Valeant Canada 17 December 2014 Retrieved 9 March 2020 via Cision Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Azilsartan amp oldid 1215294275, wikipedia, wiki, book, books, library,
