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{{Short description|Antihypertensive drug of the ACE inhibitor class}}
{{unreferenced|date=April 2008}}
{{Infobox drug
{{Drugbox
| Verifiedfields = changed
| IUPAC_name = (4''S'')-3-[(2''S'')-2-{[(2''S'')-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid
| Watchedfields = changed
| image = Imidapril structure.png
| verifiedrevid = 444377257
| CAS_number = 89371-37-9
| image = Imidapril.svg
| CAS_supplemental =
| alt =
| ATC_prefix = C09

| ATC_suffix = AA16
<!--Clinical data-->
| ATC_supplemental =
| tradename = Tanatril, others
| PubChem = 5464343
| Drugs.com = {{drugs.com|UK|imidapril-hydrochloride-5mg-tablets-leaflet}}
| DrugBank =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_category =
| routes_of_administration = [[Oral administration|By mouth]]
| ATC_prefix = C09
| ATC_suffix = AA16
| ATC_supplemental = {{ATCvet|C09|AA16}}

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = Rx-only
| legal_CA_comment =
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = Rx-only

<!--Pharmacokinetic data-->
| bioavailability = 42% (imidaprilat)
| protein_bound = 85% (imidapril),<br />53% (imidaprilat)
| metabolites = Imidaprilat (active metabolite)
| elimination_half-life = 2 hrs (imidapril),<br/>24 hrs (imidaprilat)
| excretion = 40% [[Kidney]], 50% [[bile duct]]

<!--Identifiers-->
| IUPHAR_ligand = 6377
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 89371-37-9
| PubChem = 5464343
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB11783
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BW7H1TJS22
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08068
| KEGG = D08068
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| chemical_formula =
| ChemSpiderID = 4576628
| ChEBI = 135654
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 317094
| smiles = O=C(O)[C@H]2N(C(=O)[C@@H](N[C@H](C(=O)OCC)CCc1ccccc1)C)C(=O)N(C)C2
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C20H27N3O6/c1-4-29-19(27)15(11-10-14-8-6-5-7-9-14)21-13(2)17(24)23-16(18(25)26)12-22(3)20(23)28/h5-9,13,15-16,21H,4,10-12H2,1-3H3,(H,25,26)/t13-,15-,16-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = KLZWOWYOHUKJIG-BPUTZDHNSA-N

<!--Chemical data-->
| IUPAC_name = (4''S'')-3-[(2''S'')-2-<nowiki>[[</nowiki>(2''S'')-1-ethoxy-1-oxo-4-phenylbutan-2-yl]aminopropanoyl-1-methyl-2-oxoimidazolidine-4-carboxylic acid
| C=20 | H=27 | N=3 | O=6
| C=20 | H=27 | N=3 | O=6
| melting_point = 139
| molecular_weight = 405.444 g/mol
| bioavailability =
| melting_high = 140
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category=
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| routes_of_administration =
}}
}}


<!-- Definition and medical uses -->
'''Imidapril''' (also known as Imidaprilum [INN-Latin]) is an [[ACE inhibitor]].
'''Imidapril''', sold under the brand name '''Tanatril''' among others, is an [[ACE inhibitor]] used as an [[antihypertensive]] drug and for the treatment of [[chronic heart failure]].<ref>{{cite journal | vauthors = Robinson DM, Curran MP, Lyseng-Williamson KA | title = Imidapril: a review of its use in essential hypertension, Type 1 diabetic nephropathy and chronic heart failure | journal = Drugs | volume = 67 | issue = 9 | pages = 1359–1378 | year = 2007 | pmid = 17547476 | doi = 10.2165/00003495-200767090-00008 | s2cid = 241327668 }}</ref>


<!-- Society and culture -->
It was patented in 1982 and approved for medical use in 1993.<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=469 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA469 }}</ref>


==Contraindications==
Contraindications are hypersensitivity against ACE inhibitors, especially if it has resulted in [[angioedema]]; [[idiopathic]] or [[hereditary angioedema]]; [[kidney failure]]; the second and third trimesters in pregnancy; and combination with the drug [[aliskiren]] in people with [[diabetes]].<ref name="AC" /><ref name="Arzneistoff-Profile">{{cite book|title=Arzneistoff-Profile| veditors = Dinnendahl V, Fricke U |publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2003|edition=18|volume=5|isbn=978-3-7741-9846-3|language=German}}
</ref>

==Adverse effects==
Common adverse effects are similar to other antihypertensive drugs and include headache, [[vertigo]], and [[drowsiness]]. A dry cough is common as with all ACE inhibitors.<ref name="AC" /><ref name="Arzneistoff-Profile" /> Other possible adverse effects are described at [[ACE inhibitor#Adverse effects]].

== Interactions ==

No interaction studies have been conducted except with [[digoxin]], which slightly decreases imidapril levels, possibly because it reduces its absorption from the gut. Other potential interactions are not well studied: [[Rifampicin]] reduces the activation of imidapril to its [[active metabolite]] imidaprilat. Like other ACE inhibitors, imidapril increases [[potassium]] levels in the blood and can therefore cause [[hyperkalaemia]], especially when combined with [[potassium-sparing diuretic]]s or potassium substitution. Other [[diuretic]]s, [[vasodilator]]s, [[tricyclic antidepressant]]s and [[antipsychotic]]s can add to the antihypertensive effect of imidapril. [[Lithium (medication)|Lithium]] can reach toxic levels when combined with imidapril. The effect of [[antidiabetic drug]]s can be increased, potentially causing [[hypoglycaemia]] (low blood [[glucose]] levels).<ref name="AC" /><ref name="Arzneistoff-Profile" />

==Pharmacology==
===Mechanism of action===
{{further|ACE inhibitor#Mechanism of action}}

===Pharmacokinetics===
About 70% of the ingested imidapril is absorbed quickly from the gut; this percentage is reduced significantly when taken with a fatty meal. It reaches highest [[blood plasma]] concentrations after two hours and has a [[biological half-life]] of two hours. The substance is a [[prodrug]] and is activated to imidaprilat, which reaches highest plasma concentrations after 7 hours, has an initial half-life of 7 to 9 hours and a terminal half-life of more than 24 hours. The absolute bioavailability of imidaprilat is 42%.<ref name="AC">{{cite book|title=Austria-Codex|at=Tanatril 10 mg-Tabletten|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2019|language=German}}</ref><ref name="Arzneistoff-Profile" />

About 40% of the drug is excreted via the urine and 50% via the bile and faeces.<ref name="AC" /><ref name="Arzneistoff-Profile" />

[[File:Imidaprilat.svg|thumb|left|Imidaprilat, the active metabolite]]
{{clear left}}

== References ==
{{Reflist}}


{{ACE inhibitors}}
{{ACE inhibitors}}
{{Angiotensin receptor modulators}}
{{Authority control}}


[[Category:ACE inhibitors]]
[[Category:ACE inhibitors]]
[[Category:Ethyl esters]]
[[Category:Carboxamides]]
[[Category:Amides]]
[[Category:Carboxylic acids]]
[[Category:Carboxylic acids]]
[[Category:Enantiopure drugs]]
[[Category:Ethyl esters]]
[[Category:Imidazolidinones]]
[[Category:Imidazolidinones]]
[[Category:Prodrugs]]

[[Category:Ureas]]

{{cardiovascular-drug-stub}}

[[it:Imidapril]]
[[ja:イミダプリル]]
[[pl:Imidapryl]]
[[pt:Imidapril]]
[[zh:咪达普利]]

Latest revision as of 22:53, 22 October 2023

Imidapril
Clinical data
Trade namesTanatril, others
AHFS/Drugs.comUK Drug Information
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • CA: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability42% (imidaprilat)
Protein binding85% (imidapril),
53% (imidaprilat)
MetabolitesImidaprilat (active metabolite)
Elimination half-life2 hrs (imidapril),
24 hrs (imidaprilat)
Excretion40% Kidney, 50% bile duct
Identifiers
  • (4S)-3-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]aminopropanoyl-1-methyl-2-oxoimidazolidine-4-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H27N3O6
Molar mass405.451 g·mol−1
3D model (JSmol)
Melting point139 to 140 °C (282 to 284 °F)
  • O=C(O)[C@H]2N(C(=O)[C@@H](N[C@H](C(=O)OCC)CCc1ccccc1)C)C(=O)N(C)C2
  • InChI=1S/C20H27N3O6/c1-4-29-19(27)15(11-10-14-8-6-5-7-9-14)21-13(2)17(24)23-16(18(25)26)12-22(3)20(23)28/h5-9,13,15-16,21H,4,10-12H2,1-3H3,(H,25,26)/t13-,15-,16-/m0/s1 ☒N
  • Key:KLZWOWYOHUKJIG-BPUTZDHNSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Imidapril, sold under the brand name Tanatril among others, is an ACE inhibitor used as an antihypertensive drug and for the treatment of chronic heart failure.[1]

It was patented in 1982 and approved for medical use in 1993.[2]

Contraindications

[edit]

Contraindications are hypersensitivity against ACE inhibitors, especially if it has resulted in angioedema; idiopathic or hereditary angioedema; kidney failure; the second and third trimesters in pregnancy; and combination with the drug aliskiren in people with diabetes.[3][4]

Adverse effects

[edit]

Common adverse effects are similar to other antihypertensive drugs and include headache, vertigo, and drowsiness. A dry cough is common as with all ACE inhibitors.[3][4] Other possible adverse effects are described at ACE inhibitor#Adverse effects.

Interactions

[edit]

No interaction studies have been conducted except with digoxin, which slightly decreases imidapril levels, possibly because it reduces its absorption from the gut. Other potential interactions are not well studied: Rifampicin reduces the activation of imidapril to its active metabolite imidaprilat. Like other ACE inhibitors, imidapril increases potassium levels in the blood and can therefore cause hyperkalaemia, especially when combined with potassium-sparing diuretics or potassium substitution. Other diuretics, vasodilators, tricyclic antidepressants and antipsychotics can add to the antihypertensive effect of imidapril. Lithium can reach toxic levels when combined with imidapril. The effect of antidiabetic drugs can be increased, potentially causing hypoglycaemia (low blood glucose levels).[3][4]

Pharmacology

[edit]

Mechanism of action

[edit]
Further information: ACE inhibitor § Mechanism of action

Pharmacokinetics

[edit]

About 70% of the ingested imidapril is absorbed quickly from the gut; this percentage is reduced significantly when taken with a fatty meal. It reaches highest blood plasma concentrations after two hours and has a biological half-life of two hours. The substance is a prodrug and is activated to imidaprilat, which reaches highest plasma concentrations after 7 hours, has an initial half-life of 7 to 9 hours and a terminal half-life of more than 24 hours. The absolute bioavailability of imidaprilat is 42%.[3][4]

About 40% of the drug is excreted via the urine and 50% via the bile and faeces.[3][4]

Imidaprilat, the active metabolite

References

[edit]
  1. ^ Robinson DM, Curran MP, Lyseng-Williamson KA (2007). "Imidapril: a review of its use in essential hypertension, Type 1 diabetic nephropathy and chronic heart failure". Drugs. 67 (9): 1359–1378. doi:10.2165/00003495-200767090-00008. PMID 17547476. S2CID 241327668.
  2. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 469. ISBN 978-3-527-60749-5.
  3. ^ a b c d e Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 2019. Tanatril 10 mg-Tabletten.
  4. ^ a b c d e Dinnendahl V, Fricke U, eds. (2003). Arzneistoff-Profile (in German). Vol. 5 (18 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
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