Imidapril

Antihypertensive drug of the ACE inhibitor class
  • C09AA16 (WHO) QC09AA16 (WHO)
Legal statusLegal status
  • CA: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic dataBioavailability42% (imidaprilat)Protein binding85% (imidapril),
53% (imidaprilat)MetabolitesImidaprilat (active metabolite)Elimination half-life2 hrs (imidapril),
24 hrs (imidaprilat)Excretion40% Kidney, 50% bile ductIdentifiers
  • (4S)-3-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]aminopropanoyl-1-methyl-2-oxoimidazolidine-4-carboxylic acid
CAS Number
  • 89371-37-9 checkY
PubChem CID
  • 5464343
IUPHAR/BPS
  • 6377
DrugBank
  • DB11783 checkY
ChemSpider
  • 4576628 ☒N
UNII
  • BW7H1TJS22
KEGG
  • D08068 checkY
ChEBI
  • CHEBI:135654
ChEMBL
  • ChEMBL317094 ☒N
CompTox Dashboard (EPA)
  • DTXSID2048242 Edit this at Wikidata
Chemical and physical dataFormulaC20H27N3O6Molar mass405.451 g·mol−13D model (JSmol)
  • Interactive image
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

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

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

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

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%.[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

  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.
  • v
  • t
  • e
ACE inhibitors
("-pril")AIIRAs
("-sartan")Renin inhibitors
("-kiren")Dual ACE/NEP inhibitors
Neprilysin inhibitors
  • v
  • t
  • e
ATRTooltip Angiotensin receptor
Combinations:
Authority control databases: National Edit this at Wikidata
  • Czech Republic