Tìm theo
Trandolapril
Các tên gọi khác (2) :
  • Mavik
  • Trandolaprilum
angiotensin converting enzyme inhibitors, antihypertensive agents
Thuốc Gốc
Small Molecule
CAS: 87679-37-6
ATC: C09AA10
ĐG : Abbott Laboratories Ltd. , http://www.abbott.com
CTHH: C24H34N2O5
PTK: 430.5372
Trandolapril is a non-sulhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to its biologically active diacid form, trandolaprilat, in the liver. Trandolaprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Trandolapril may be used to treat mild to moderate hypertension, to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction, as an adjunct treatment for congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H34N2O5
Phân tử khối
430.5372
Monoisotopic mass
430.246772208
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
InChI Key
InChIKey=VXFJYXUZANRPDJ-WTNASJBWSA-N
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
Traditional IUPAC Name
trandolapril
SMILES
[H][C@@]12C[C@H](N(C(=O)[C@H](C)N[C@@H](CCC3=CC=CC=C3)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O
Độ tan chảy
119-123 °C
Độ hòa tan
2.07e-02 g/l
logP
3.5
logS
-4.3
pKa (strongest acidic)
3.8
pKa (Strongest Basic)
5.21
PSA
95.94 Å2
Refractivity
115.79 m3·mol-1
Polarizability
46.79 Å3
Rotatable Bond Count
10
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : Trandolapril is a non-sulhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to its biologically active diacid form, trandolaprilat, in the liver. Trandolaprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Trandolapril may be used to treat mild to moderate hypertension, to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction, as an adjunct treatment for congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy. 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.
Dược Động Học :
▧ Absorption :
~ 40-60% absorbed; extensive first pass metabolism results in a low bioavailability of 4-14%
▧ Volume of Distribution :
* 18 L
▧ 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).
▧ Metabolism :
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]
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • 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.
  • Allopurinol The ACE inhibitor, Trandolapril, may increase the risk of hypersensitivity reactions to Allopurinol.
  • 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.
  • Amiloride Increased risk of hyperkalemia. Monitor serum potassium levels.
  • 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.
  • Azathioprine Trandolapril may increase the risk of neutropenia. Monitor for increased toxic effects of Azathioprine if Trandolapril is initiated or dose increased.
  • Azilsartan medoxomil Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
  • 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.
  • Benzphetamine Benzphetamine may reduce the efficacy of Trandolapril.
  • Bumetanide The loop diuretic, Bumetanide, may increase the hypotensive effect of Trandolapril. Bumetanide may also increase the nephrotoxicity of Trandolapril.
  • Candesartan The angiotensin II receptor blocker, Candesartan, may increase the adverse effects of Trandolapril.
  • 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.
  • 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.
  • 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.
  • Cyclosporine The ACE inhibitor, Trandolapril, may increase the nephrotoxicity of Cyclosporine.
  • Dextroamphetamine Dextroamphetamine may reduce the efficacy of Trandolapril.
  • Diazoxide Diazoxide may increase the hypotensive effect of Trandolapril. Monitor for changes in blood pressure.
  • 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.
  • 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.
  • Drospirenone Increased risk of hyperkalemia. Monitor serum potassium levels.
  • Ephedra Ephedra may antagonize the antihypertensive effect of Trandolapril. Monitor Trandolapril efficacy.
  • Eplerenone Increased risk of hyperkalemia. Monitor serum potassium levels.
  • Epoprostenol The prostacyclin analogue, Epoprostenol, may increase the hypotensive effect of Trandolapril.
  • Eprosartan The angiotensin II receptor blocker, Eprosartan, may increase the adverse effects of Trandolapril.
  • Ethacrynic acid The loop diuretic, Ethacrynic acid, may increase the hypotensive effect of Trandolapril. Ethacrynic acid may also increase the nephrotoxicity of Trandolapril.
  • 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.
  • 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.
  • 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.
  • Furosemide The loop diuretic, Furosemide, may increase the hypotensive effect of Trandolapril. Furosemide may also increase the nephrotoxicity of Trandolapril.
  • Ginseng Ginseng may antagonize the antihypertensive effect of Trandolapril. Monitor Trandolapril efficacy.
  • 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.
  • 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.
  • 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.
  • Icatibant Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
  • Iloprost The prostacyclin analogue, Iloprost, may increase the hypotensive effect of Trandolapril.
  • 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.
  • 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.
  • Irbesartan The angiotensin II receptor blocker, Irbesartan, may increase the adverse effects 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.
  • 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.
  • Lisdexamfetamine Lisdexamfetamine may reduce the efficacy 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.
  • Losartan The angiotensin II receptor blocker, Losartan, may increase the adverse effects of Trandolapril.
  • 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.
  • 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.
  • 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.
  • 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.
  • Methamphetamine Methamphetamine may reduce the efficacy of Trandolapril.
  • 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.
  • Methylphenidate Methylphenidate may antagonize the antihypertensive effect of Trandolapril. Monitor for changes in blood pressure if Methylphenidate 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.
  • 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.
  • 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.
  • Olmesartan The angiotensin II receptor blocker, Olmesartan, may increase the adverse effects of Trandolapril.
  • 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.
  • Phendimetrazine Phendimetrazine may reduce the efficacy of Trandolapril.
  • Phentermine Phentermine may reduce the efficacy 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.
  • 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.
  • Potassium Increased risk of hyperkalemia
  • Potassium Chloride The potassium salt may increase the hyperkalemic effect of Trandolapril.
  • Quinine May cause additive hypotensive effects. Monitor for changes in blood pressure if Quinine is initiated, discontinued or dose changed.
  • Rituximab Trandolapril may incresae the hypotensive effect of Rituximab.
  • Salsalate The salicylate, Salsalate, may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Salsalate is initiated, discontinued or dose changed.
  • Sirolimus Increased risk of angioedema. Monitor for signs and symptoms of facial and systemic edema and/or erythema.
  • Sodium bicarbonate Sodium bicarbonate may decrease the absorption of Trandolapril. Administration should be spaced.
  • Spironolactone Increased risk of hyperkalemia. Monitor serum potassium levels.
  • 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.
  • Telmisartan The angiotensin II receptor blocker, Telmisartan, may increase the adverse effects of Trandolapril.
  • Temsirolimus Increased risk of angioedema. Monitor for signs and symptoms of facial and systemic edema and/or erythema.
  • 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.
  • Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
  • 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.
  • Torasemide The loop diuretic, Torasemide, may increase the hypotensive effect of Trandolapril. Torasemide may also increase the nephrotoxicity of Trandolapril.
  • Treprostinil The prostacyclin analogue, Treprostinil, may increase the hypotensive effect of Trandolapril.
  • Triamterene 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.
  • Trimethoprim Increased risk of hyperkalemia. Monitor serum potassium levels.
  • Valsartan The angiotensin II receptor blocker, Valsartan, may increase the adverse effects of Trandolapril.
Liều Lượng & Cách Dùng : Capsule - Oral - 0.5 mg
Capsule - Oral - 1 mg
Capsule - Oral - 2 mg
Capsule - Oral - 4 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Abbott
    Sản phẩm biệt dược : Mavik
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00519
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5484727
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508300
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00383
ChemSpider
http://www.chemspider.com/Chemical-Structure.4588590.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/65862-164-01
PharmGKB
http://www.pharmgkb.org/drug/PA451737
Wikipedia
http://en.wikipedia.org/wiki/Trandolapril
RxList
http://www.rxlist.com/cgi/generic3/mavik.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tar1425.shtml
Drugs.com
http://www.drugs.com/cdi/trandolapril.html
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