QuickView for Trandolapril (compound)

Summary
General Info

PubChem

PubChem Compound 5484727

Name:	trandolapril
PubChem Compound ID:	5484727
Molecular formula:	C₂₄H₃₄N₂O₅
Molecular weight:	430.537 g/mol
Synonyms:	Trandolaprilum [Latin]; Preran; 1H-Indole-2-carboxylic acid, 1-((2S)-2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydro-, (2S,3aR,7aS)-; Mavik (TN); (2S,3aR,7aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)hexahydro-2-indolinecarboxylic acid, 1-ethyl ester; Trandolapril [BAN:INN]; Gopten; Trandolapril; Mavik; D00383. show more » Trandolaprilum [Latin]; Preran; 1H-Indole-2-carboxylic acid, 1-((2S)-2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydro-, (2S,3aR,7aS)-; Mavik (TN); (2S,3aR,7aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)hexahydro-2-indolinecarboxylic acid, 1-ethyl ester; Trandolapril [BAN:INN]; Gopten; Trandolapril; Mavik; D00383; Trandolapril (JAN); 87679-37-6; 1H-Indole-2-carboxylic acid, octahydro-1-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)-, (2S-(1(R(R)),2-alpha,3a-alpha,7a-beta))-; RU 44570; RU-44570; Odrik; Udrik; CCRIS 6594 show less «

DrugBank

Identification

Name:	trandolapril
Name (isomeric):	DB00519
Drug Type:	small molecule
Synonyms:	Trandolaprilum [Latin]
Brand:	Mavik
Brand name mixture:	Tarka(trandolapril + verapamil hydrochloride)
Category:	Angiotensin-converting Enzyme Inhibitors, Antihypertensive Agents
CAS number:	87679-37-6

Pharmacology

Indication:	For the treatment of mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure (CHF), to improve survival following myocardial infarction (MI) in individuals who are hemodynamically stable and demonstrate symptoms of left ventricular systolic dysfunction or signs of CHF within a few days following acute MI, and to slow progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.
Pharmacology:	Trandolapril is the ethyl ester prodrug of a nonsulfhydryl ACE inhibitor, trandolaprilat. Trandolapril is deesterified in the liver to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE than its parent compound. ACE is a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostati... show more » Trandolapril is the ethyl ester prodrug of a nonsulfhydryl ACE inhibitor, trandolaprilat. Trandolapril is deesterified in the liver to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE than its parent compound. ACE is a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure via a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of trandolaprilat by causing increased vasodilation and decreased blood pressure. The blood pressure lowering effect of trandolaprilat is due to a decrease in peripheral vascular resistance, which is not accompanied by significant changes in urinary excretion of chloride or potassium or water or sodium retention. show less «
Mechanism of Action:	There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, w... show more » There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Trandolaprilat, the active metabolite of trandolapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Trandolaprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. show less «
Absorption:	~ 40-60% absorbed; extensive first pass metabolism results in a low bioavailability of 4-14%
Protein binding:	Serum protein binding of trandolapril is ~ 80% (independent of concentration and not saturable) while that of trandolaprilat is 65 to 94% (concentration-dependent and saturable).
Biotransformation:	Cleavage of the ester group of trandolapril, primarily in the liver, is responsible for conversion to trandolaprilat, the active metabolite. Seven other metabolites, including diketopiperazine and glucuronide conjugated derivatives of trandolapril and trandolaprilat, have been identified.
Route of elimination:	After oral administration of trandolapril, about 33% of parent drug and metabolites are recovered in urine, mostly as trandolaprilat, with about 66% in feces.
Half Life:	The elimination half lives of trandolapril and trandolaprilat are about 6 and 10 hours, respectively, but, similar to all ACE inhibitors, trandolaprilat also has a prolonged terminal elimination phase that involves a small fraction of administered drug. This likely represents drug binding to plasma and tissue ACE. The effective half life of elimination for trandolaprilat is 16-24 hours.
Clearance:	52 L/h [After approximately 2 mg IV doses]
Toxicity:	Most likely clinical manifestations of overdose are symptoms of severe hypotension. Most common adverse effects include cough, headache and dizziness. The oral LD₅₀ of trandolapril in mice was 4875 mg/kg in males and 3990 mg/kg in females. In rats, an oral dose of 5000 mg/kg caused low mortality (1 male out of 5; 0 females). In dogs, an oral dose of 1000 mg/kg did not cause mortality and abnormal clinical signs were not observed.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Herbs that may attenuate the antihypertensive effect of trandolapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.

High salt intake may attenuate the antihypertensive effect of trandolapril.

Take without regard to meals.

Trandolapril may decrease the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.

Drug interaction:

Epoprostenol	The prostacyclin analogue, Epoprostenol, may increase the hypotensive effect of Trandolapril.
Chlorothiazide	The thiazide diuretic, Chlorothiazide, may increase the hypotensive effect of Trandolapril. Chlorothiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Polythiazide	The thiazide diuretic, Polythiazide, may increase the hypotensive effect of Trandolapril. Polythiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Candesartan	The angiotensin II receptor blocker, Candesartan, may increase the adverse effects of Trandolapril.
Hydroflumethiazide	The thiazide diuretic, Hydroflumethiazide, may increase the hypotensive effect of Trandolapril. Hydroflumethiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.

Epoprostenol	The prostacyclin analogue, Epoprostenol, may increase the hypotensive effect of Trandolapril.
Chlorothiazide	The thiazide diuretic, Chlorothiazide, may increase the hypotensive effect of Trandolapril. Chlorothiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Polythiazide	The thiazide diuretic, Polythiazide, may increase the hypotensive effect of Trandolapril. Polythiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Candesartan	The angiotensin II receptor blocker, Candesartan, may increase the adverse effects of Trandolapril.
Hydroflumethiazide	The thiazide diuretic, Hydroflumethiazide, may increase the hypotensive effect of Trandolapril. Hydroflumethiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Lumiracoxib	The NSAID, Lumiracoxib, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Lumiracoxib is initiated, discontinued or dose changed.
Tolmetin	The NSAID, Tolmetin, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Tolmetin is initiated, discontinued or dose changed.
Mefenamic acid	The NSAID, Mefenamic acid, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Mefenamic acid is initiated, discontinued or dose changed.
Azathioprine	Trandolapril may increase the risk of neutropenia. Monitor for increased toxic effects of Azathioprine if Trandolapril is initiated or dose increased.
Oxaprozin	The NSAID, Oxaprozin, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Oxaprozin is initiated, discontinued or dose changed.
Trimethoprim	Increased risk of hyperkalemia. Monitor serum potassium levels.
Benzphetamine	Benzphetamine may reduce the efficacy of Trandolapril.
Sulindac	The NSAID, Sulindac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Sulindac is initiated, discontinued or dose changed.
Metolazone	The thiazide diuretic, Metolazone, may increase the hypotensive effect of Trandolapril. Metolazone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Tizanidine	Tizanidine increases the risk of hypotension with the ACE inhibitor
Celecoxib	The NSAID, Celecoxib, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Celecoxib is initiated, discontinued or dose changed.
Ibuprofen	The NSAID, Ibuprofen, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Ibuprofen is initiated, discontinued or dose changed.
Lisdexamfetamine	Lisdexamfetamine may reduce the efficacy of Trandolapril.
Treprostinil	The prostacyclin analogue, Treprostinil, may increase the hypotensive effect of Trandolapril.
Lithium	Trandolapril may increase the serum concentration of Lithium increasing the risk of Lithium toxicity. Monitor for changes in Lithium serum concentrations, toxicity and efficacy if Trandolapril is initiated, discontinued or dose changed.
Methylphenidate	Methylphenidate may antagonize the antihypertensive effect of Trandolapril. Monitor for changes in blood pressure if Methylphenidate is initiated, discontinued or dose changed.
Fenoprofen	The NSAID, Fenoprofen, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Fenoprofen is initiated, discontinued or dose changed.
Furosemide	The loop diuretic, Furosemide, may increase the hypotensive effect of Trandolapril. Furosemide may also increase the nephrotoxicity of Trandolapril.
Ketoprofen	The NSAID, Ketoprofen, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Ketoprofen is initiated, discontinued or dose changed.
Telmisartan	The angiotensin II receptor blocker, Telmisartan, may increase the adverse effects of Trandolapril.
Triamterene	Increased risk of hyperkalemia. Monitor serum potassium levels.
Indomethacin	The NSAID, Indomethacin, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Indomethacin is initiated, discontinued or dose changed.
Tiaprofenic acid	The NSAID, Tiaprofenic acid, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Tiaprofenic acid is initiated, discontinued or dose changed.
Iloprost	The prostacyclin analogue, Iloprost, may increase the hypotensive effect of Trandolapril.
Chlorthalidone	The thiazide diuretic, Chlorthalidone, may increase the hypotensive effect of Trandolapril. Chlorthalidone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Hydrochlorothiazide	The thiazide diuretic, Hydrochlorothiazide, may increase the hypotensive effect of Trandolapril. Hydrochlorothiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Indapamide	The thiazide diuretic, Indapamide, may increase the hypotensive effect of Trandolapril. Indapamide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Temsirolimus	Increased risk of angioedema. Monitor for signs and symptoms of facial and systemic edema and/or erythema.
Methyclothiazide	The thiazide diuretic, Methyclothiazide, may increase the hypotensive effect of Trandolapril. Methyclothiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Phendimetrazine	Phendimetrazine may reduce the efficacy of Trandolapril.
Naproxen	The NSAID, Naproxen, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Naproxen is initiated, discontinued or dose changed.
Etodolac	The NSAID, Etodolac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Etodolac is initiated, discontinued or dose changed.
Spironolactone	Increased risk of hyperkalemia. Monitor serum potassium levels.
Amiloride	Increased risk of hyperkalemia. Monitor serum potassium levels.
Phentermine	Phentermine may reduce the efficacy of Trandolapril.
Nabumetone	The NSAID, Nabumetone, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Nabumetone is initiated, discontinued or dose changed.
Acetylsalicylic acid	Acetylsalicylic acid may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Acetylsalicylic acid is initiated, discontinued or dose changed.
Meclofenamic acid	The NSAID, Meclofenamate, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Meclofenamate is initiated, discontinued or dose changed.
Aminosalicylic Acid	The salicylate, Aminosalicylic acid, may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Aminosalicylic acid is initiated, discontinued or dose changed.
Ethacrynic acid	The loop diuretic, Ethacrynic acid, may increase the hypotensive effect of Trandolapril. Ethacrynic acid may also increase the nephrotoxicity of Trandolapril.
Ephedra	Ephedra may antagonize the antihypertensive effect of Trandolapril. Monitor Trandolapril efficacy.
Potassium Chloride	The potassium salt may increase the hyperkalemic effect of Trandolapril.
Dextroamphetamine	Dextroamphetamine may reduce the efficacy of Trandolapril.
Ginseng	Ginseng may antagonize the antihypertensive effect of Trandolapril. Monitor Trandolapril efficacy.
Losartan	The angiotensin II receptor blocker, Losartan, may increase the adverse effects of Trandolapril.
Bendroflumethiazide	The thiazide diuretic, Bendroflumethiazide, may increase the hypotensive effect of Trandolapril. Bendroflumethiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Amifostine	Trandolapril may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Trandolapril should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Salsalate	The salicylate, Salsalate, may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Salsalate is initiated, discontinued or dose changed.
Cyclosporine	The ACE inhibitor, Trandolapril, may increase the nephrotoxicity of Cyclosporine.
Diazoxide	Diazoxide may increase the hypotensive effect of Trandolapril. Monitor for changes in blood pressure.
Flurbiprofen	The NSAID, Flurbiprofen, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Flurbiprofen is initiated, discontinued or dose changed.
Allopurinol	The ACE inhibitor, Trandolapril, may increase the risk of hypersensitivity reactions to Allopurinol.
Sodium bicarbonate	Sodium bicarbonate may decrease the absorption of Trandolapril. Administration should be spaced.
Irbesartan	The angiotensin II receptor blocker, Irbesartan, may increase the adverse effects of Trandolapril.
Piroxicam	The NSAID, Piroxicam, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Piroxicam is initiated, discontinued or dose changed.
Sirolimus	Increased risk of angioedema. Monitor for signs and symptoms of facial and systemic edema and/or erythema.
Olmesartan	The angiotensin II receptor blocker, Olmesartan, may increase the adverse effects of Trandolapril.
Torasemide	The loop diuretic, Torasemide, may increase the hypotensive effect of Trandolapril. Torasemide may also increase the nephrotoxicity of Trandolapril.
Potassium	Increased risk of hyperkalemia
Diflunisal	The NSAID, Diflunisal, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Diflunisal is initiated, discontinued or dose changed.
Bumetanide	The loop diuretic, Bumetanide, may increase the hypotensive effect of Trandolapril. Bumetanide may also increase the nephrotoxicity of Trandolapril.
Rituximab	Trandolapril may incresae the hypotensive effect of Rituximab.
Drospirenone	Increased risk of hyperkalemia. Monitor serum potassium levels.
Trichlormethiazide	The thiazide diuretic, Trichlormethiazide, may increase the hypotensive effect of Trandolapril. Trichlormethiazide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Diclofenac	The NSAID, Diclofenac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Diclofenac is initiated, discontinued or dose changed.
Ketorolac	The NSAID, Ketorolac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Ketorolac is initiated, discontinued or dose changed.
Meloxicam	The NSAID, Meloxicam, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Meloxicam is initiated, discontinued or dose changed.
Eplerenone	Increased risk of hyperkalemia. Monitor serum potassium levels.
Methamphetamine	Methamphetamine may reduce the efficacy of Trandolapril.
Quinine	May cause additive hypotensive effects. Monitor for changes in blood pressure if Quinine is initiated, discontinued or dose changed.
Eprosartan	The angiotensin II receptor blocker, Eprosartan, may increase the adverse effects of Trandolapril.
Valsartan	The angiotensin II receptor blocker, Valsartan, may increase the adverse effects of Trandolapril.

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Targets

Angiotensin-converting enzyme

Transporters

Oligopeptide transporter, small intestine isoform

Oligopeptide transporter, kidney isoform