Trandolapril

Antihypertensive drug of the ACE inhibitor class

C09AA10 (WHO)

In general: ℞ (Prescription only)

Pharmacokinetic dataProtein bindingTrandolapril 80%
(independent of concentration)
Trandolaprilat 65 to 94%
(concentration-dependent)MetabolismLiverElimination half-life6 hours (trandolapril)
10 hours (trandolaprilat)ExcretionFecal and KidneyIdentifiers

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

87679-37-6^Y

PubChem CID

5484727

IUPHAR/BPS

6453

DrugBank

DB00519^Y

ChemSpider

4588590^Y

UNII

1T0N3G9CRC

KEGG

D00383^Y

ChEBI

CHEBI:9649

ChEMBL

ChEMBL1519^Y

CompTox Dashboard (EPA)

DTXSID2023692

ECHA InfoCard100.108.532

Chemical and physical dataFormulaC₂₄H₃₄N₂O₅Molar mass430.545 g·mol⁻¹3D model (JSmol)

Interactive image

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)

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 ramipril but has a cyclohexane group. It is a prodrug that must be metabolized into its active form. It has a longer half-life when compared to other agents in this class.

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

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 deesterified to trandolaprilat. It is believed to exert its antihypertensive effect through the renin–angiotensin–aldosterone system. Trandolapril has a half-life of about six hours, while trandolaprilat has a half life of about ten hours. 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

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

^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 469. ISBN 9783527607495.
^ Tan X, He W, Liu Y (December 2009). "Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in obstructive nephropathy". Kidney International. 76 (12): 1248–1257. doi:10.1038/ki.2009.346. PMC 5527548. PMID 19759524.

External links

Trandolapril Information - rxlist.com (Rxlist.com, The Internet Drug Index)

Antihypertensive drugs acting on the renin–angiotensin system (C09)

ACE inhibitors
("-pril")

AIIRAs
("-sartan")

Azilsartan
Candesartan
Eprosartan
Fimasartan
Irbesartan (+HCT)
Losartan (+HCT)
Olmesartan (+amlodipine, +amlodipine and HCT, +HCT)
Tasosartan^§
Telmisartan (+amlodipine, +HCT)
Valsartan (+amlodipine, +amlodipine and HCT, +HCT, +nebivolol)

Renin inhibitors
("-kiren")

Aliskiren (+amlodipine, +HCT, +amlodipine and HCT)
Remikiren^§

Dual ACE/NEP inhibitors

Gemopatrilat
Ilepatril
Omapatrilat
Sampatrilat

Neprilysin inhibitors

Sacubitril (+valsartan)

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

v t e Angiotensin receptor modulators
ATRTooltip Angiotensin receptor	Agonists: Angiotensin II Angiotensin III Angiotensin IV L-163,491 Saralasin Antagonists: Abitesartan Azilsartan Candesartan Elisartan Embusartan Eprosartan EXP-3174 Fimasartan Forasartan Irbesartan Losartan Milfasartan Olmesartan Olodanrigan PD123319 Pomisartan Pratosartan Ripisartan Saprisartan Sparsentan Tasosartan Telmisartan Valsartan Zolasartan ACE inhibitors: Alacepril Benazepril Captopril Cilazapril Delapril Enalapril Enalaprilat Fosinopril Gemopatrilat Imidapril Lisinopril Moexipril Omapatrilat Perindopril Quinapril Quinaprilat Ramipril Rentiapril Rescinnamine Spirapril Spiraprilat Temocapril Trandolapril Zofenopril Zofenoprilat Renin inhibitors: Aliskiren Ciprokiren Ditekiren Enalkiren Imarikiren Pepstatin Remikiren Terlakiren Zankiren Propeptides: Angiotensinogen Angiotensin I
Combinations:	Amlodipine/valsartan Olmesartan/amlodipine Olmesartan/amlodipine/hydrochlorothiazide Valsartan/hydrochlorothiazide Valsartan/hydrochlorothiazide/amlodipine

Angiotensin receptor modulators

ATRTooltip Angiotensin receptor