Trandolapril

Trandolapril is an ACE inhibitor used to treat high blood pressure. It may also be used to treat other conditions. It is similar in structure to another ACE Inhibitor, Ramipril but has a cyclohexane group. It also is a pro-drug and must get metabolized. It has an extended half-life and therefore has a higher potency.

Trandolapril
Clinical data
Trade namesMavik, others
AHFS/Drugs.comMonograph
MedlinePlusa697010
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein bindingTrandolapril 80%
(independent of concentration)
Trandolaprilat 65 to 94%
(concentration-dependent)
MetabolismLiver
Elimination half-life6 hours (trandolapril)
10 hours (trandolaprilat)
ExcretionFecal and Kidney
Identifiers
IUPAC name
  • (2S,3aR,7aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydro-1H-indole-2-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.108.532
Chemical and physical data
FormulaC24H34N2O5
Molar mass430.545 g·mol−1
3D model (JSmol)
Melting point119 to 123 °C (246 to 253 °F)
SMILES
  • O=C(OCC)[C@@H](N[C@H](C(=O)N1[C@H](C(=O)O)C[C@H]2CCCC[C@H]12)C)CCc3ccccc3
InChI
  • InChI=1S/C24H34N2O5/c1-3-31-24(30)19(14-13-17-9-5-4-6-10-17)25-16(2)22(27)26-20-12-8-7-11-18(20)15-21(26)23(28)29/h4-6,9-10,16,18-21,25H,3,7-8,11-15H2,1-2H3,(H,28,29)/t16-,18+,19-,20-,21-/m0/s1 Y
  • Key:VXFJYXUZANRPDJ-WTNASJBWSA-N Y
  (verify)

It was patented in 1981, and approved for medical use in 1993.[1] It is marketed by Abbott Laboratories under the brand name Mavik.

Side effects

Side effects reported for trandolapril include nausea, vomiting, diarrhea, headache, dry cough, dizziness or lightheadedness when sitting up or standing, hypotension, or fatigue.

Possible drug interactions

Patients also on diuretics may experience an excessive reduction of blood pressure after initiation of therapy with trandolapril. It can reduce potassium loss caused by thiazide diuretics, and increase serum potassium when used alone. Therefore, hyperkalemia is a possible risk. Increased serum lithium levels can occur in patients who are also on lithium.

Contraindications and precautions
Main article: ACE inhibitor § Contraindications and precautions

Pregnancy and lactation

Trandolapril is teratogenic (US: pregnancy category D) and can cause birth defects and even death of the developing fetus. The highest risk to the fetus is during the second and third trimesters. When pregnancy is detected, trandolapril should be discontinued as soon as possible. Trandolapril should not be administered to nursing mothers.

Additional effects

Combination therapy with paricalcitol and trandolapril has been found to reduce fibrosis in obstructive uropathy.[2]

Pharmacology
Trandolaprilat — the active metabolite of trandolapril

Trandolapril is a prodrug that is de-esterified to trandolaprilat. It is believed to exert its antihypertensive effect through the renin–angiotensin–aldosterone system. Trandolapril has a half-life of about 6 hours, and trandolaprilat has a half life of about 10 h. Trandolaprilat has about eight times the activity of its parent drug. About one-third of trandolapril and its metabolites are excreted in the urine, and about two-thirds of trandolapril and its metabolites are excreted in the feces. Serum protein binding of trandolapril is about 80%.

Mode of action
Main article: ACE inhibitor

Trandolapril acts by competitive inhibition of angiotensin converting enzyme (ACE), a key enzyme in the renin–angiotensin system which plays an important role in regulating blood pressure.

References
  1. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 469. ISBN 9783527607495.
  2. Tan X, He W, Liu Y (December 2009). "Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in obstructive nephropathy". Kidney International. 76 (12): 1248–57. doi:10.1038/ki.2009.346. PMC 5527548. PMID 19759524.
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