Peringatan Keamanan

Symptoms of overdose may include excessive peripheral vasodilation (with marked hypotension and shock), bradycardia, electrolyte disturbances, and renal failure. Cases of ACE inhibitor induced hepatotoxicity have been reported in humans and presented as acute jaundice and elevated liver enzymes.^A174280 Removal of the ACE inhbitor resulted in a decline in liver enzymes and re-challenge produced a subsequent increase.

There were no observed tumerogenic effects at chronic doses up to 500mg/kg/day to rats for 24 months or at doses up to 1000mg/kg/day to mice for 18 months. For both species doses were administered by gavage and equivalent to 200 time the maximum recommended human exposure based on body surface area.

No mutagenic activity was detected in the Ames test in bacteria, the micronucleus test in mice, unscheduled DNA synthesis in a human cell line, or a forward gene-mutation assay in a Chinese hamster ovary cell line. Several metabolites of ramipril also produced negative results in the Ames test.

No effects on fertility were seen in rats at doses up to 500mg/kg/day. No teratogenicity was observed in rats and cynomolgus monkeys at doses 400 times the maximum recommended human exposure nor in rabbites at 2 times the maximum recommended human exposure.

LD₅₀ 10 g/kg (rat).MSDS
LD₅₀ 10.5 g/kg (mouse).MSDS
LD₅₀ 1 g/kg (dog).MSDS

Ramipril

DB00178

small molecule approved

Deskripsi

Ramipril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to ramiprilat in the liver and, to a lesser extent, kidneys. Ramiprilat is a potent, competitive inhibitor of 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). Ramipril may be used in the treatment of hypertension, congestive heart failure, nephropathy, and to reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events.

Struktur Molekul 2D

Berat 416.5106

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) Plasma concentrations of ramiprilat decline in a triphasic manner.[FDA Label] Initial rapid decline represents distribution into tissues and has a half life of 2-4 hours. The half life of the apparent elimination phase is 9-18 hours, which is thought to represent clearance of free drug. The half-life of the terminal elimination phase is > 50 hours and thought to represent clearance of drug bound to ACE due to its slow dissociation. The half life of ramiprilat after multiple daily doses (MDDs) is dose-dependent, ranging from 13-17 hours with 5-10 mg MDDs to 27-36 hours for 2.5 mg MDDs.

Volume Distribusi -

Klirens (Clearance) The renal clearance of ramipril and ramiprilat was reported to be 7.2 and 77.4 mL/min/1.73m<sup>2</sup>. [A174595] The mean renal clearance of ramipril and ramiprilat is reported to be 10.7 and 126.8 mL/min in healthy elderly patients with normal renal function, additionally the Cmax of ramiprilat is approximately 20% higher in this population. While the pharmacokinetics of ramipril appear unaffected by reduced renal function, the plasma concentration and half-life of ramiprilat are increased. In patient's with hepatic failure the concentration of ramipril is initially increased while the tmax of ramiprilat is prolonged due to a reduced ability to metabolize the drug. However, steady state concentrations of ramiprilat are the same in hepatic failure as in healthy patients.

Absorpsi

The extent of absorption is at least 50-60%.FDA Label. Food decreases the rate of absorption from the GI tract without affecting the extent of absorption. The absolute bioavailabilities of ramipril and ramiprilat were 28% and 44%, respectively, when oral administration was compared to intravenous administration. The serum concentration of ramiprilat was unchanged when capsules were opened and the contents dissolved in water, dissolved in apple juice, or suspended in apple sauce.

Metabolisme

Hepatic metabolism accounts for 75% of total ramipril metabolism.FDA Label 25% of hepatic metabolism produces the active metabolite ramiprilat via liver esterase enzymes. 100% of renal metabolism converts ramipril to ramiprilat. Other metabolites, diketopiperazine ester, the diketopiperazine acid, and the glucuronides of ramipril and ramiprilat, are inactive.

Rute Eliminasi

Following oral administration, about 60% of the dose is eliminated in the urine as unchanged ramipril (<2%) and its metabolites. About 40% of the dose is found in the feces, representing both unabsorbed drug and drugs and metabolites eliminated via biliary excretion. The urinary excretion of ramipril may be reduced in patients with impaired renal function.^L12798

Farmakogenomik

1 Varian

ACE (rs4344)

Patients with this genotype have a shorter time to lowering of blood pressure with ramipril

Interaksi Makanan

2 Data

1. Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
2. Take with or without food. The absorption is unaffected by food.

Interaksi Obat

843 Data

Duloxetine	The risk or severity of orthostatic hypotension and syncope can be increased when Ramipril is combined with Duloxetine.
Levodopa	The risk or severity of hypotension and orthostatic hypotension can be increased when Ramipril is combined with Levodopa.
Risperidone	Ramipril may increase the hypotensive activities of Risperidone.
Alfuzosin	Alfuzosin may increase the hypotensive activities of Ramipril.
Amifostine	Ramipril may increase the hypotensive activities of Amifostine.
Diazoxide	Diazoxide may increase the hypotensive activities of Ramipril.
Methylphenidate	Methylphenidate may decrease the antihypertensive activities of Ramipril.
Dexmethylphenidate	Dexmethylphenidate may decrease the antihypertensive activities of Ramipril.
Obinutuzumab	Ramipril may increase the hypotensive activities of Obinutuzumab.
Pentoxifylline	Pentoxifylline may increase the hypotensive activities of Ramipril.
Rituximab	Ramipril may increase the hypotensive activities of Rituximab.
Desmopressin	Desmopressin may decrease the antihypertensive activities of Ramipril.
Phentermine	Phentermine may decrease the antihypertensive activities of Ramipril.
Midodrine	Midodrine may decrease the antihypertensive activities of Ramipril.
Eletriptan	Eletriptan may decrease the antihypertensive activities of Ramipril.
Isoetharine	Isoetharine may decrease the antihypertensive activities of Ramipril.
Methysergide	Methysergide may decrease the antihypertensive activities of Ramipril.
Cabergoline	Cabergoline may decrease the antihypertensive activities of Ramipril.
Atomoxetine	Atomoxetine may decrease the antihypertensive activities of Ramipril.
Etomidate	Etomidate may decrease the antihypertensive activities of Ramipril.
Zolmitriptan	Zolmitriptan may decrease the antihypertensive activities of Ramipril.
Dihydroergotamine	Dihydroergotamine may decrease the antihypertensive activities of Ramipril.
Protriptyline	Protriptyline may decrease the antihypertensive activities of Ramipril.
Methylergometrine	Methylergometrine may decrease the antihypertensive activities of Ramipril.
Norepinephrine	Norepinephrine may decrease the antihypertensive activities of Ramipril.
Mirtazapine	Mirtazapine may decrease the antihypertensive activities of Ramipril.
Phenylephrine	Phenylephrine may decrease the antihypertensive activities of Ramipril.
Phenylpropanolamine	Phenylpropanolamine may decrease the antihypertensive activities of Ramipril.
Droperidol	Droperidol may decrease the antihypertensive activities of Ramipril.
Buspirone	Buspirone may decrease the antihypertensive activities of Ramipril.
Doxapram	Doxapram may decrease the antihypertensive activities of Ramipril.
Lisuride	Lisuride may decrease the antihypertensive activities of Ramipril.
Metaraminol	Metaraminol may decrease the antihypertensive activities of Ramipril.
Trazodone	Trazodone may decrease the antihypertensive activities of Ramipril.
Epinephrine	Epinephrine may decrease the antihypertensive activities of Ramipril.
Sumatriptan	Sumatriptan may decrease the antihypertensive activities of Ramipril.
Ergotamine	Ergotamine may decrease the antihypertensive activities of Ramipril.
Nicergoline	Nicergoline may decrease the antihypertensive activities of Ramipril.
Methoxamine	Methoxamine may decrease the antihypertensive activities of Ramipril.
Trimipramine	Trimipramine may decrease the antihypertensive activities of Ramipril.
Alfentanil	Alfentanil may decrease the antihypertensive activities of Ramipril.
Fentanyl	Fentanyl may decrease the antihypertensive activities of Ramipril.
Orciprenaline	Orciprenaline may decrease the antihypertensive activities of Ramipril.
Phenmetrazine	Phenmetrazine may decrease the antihypertensive activities of Ramipril.
Trifluoperazine	Trifluoperazine may decrease the antihypertensive activities of Ramipril.
Dobutamine	Dobutamine may decrease the antihypertensive activities of Ramipril.
Pseudoephedrine	Pseudoephedrine may decrease the antihypertensive activities of Ramipril.
Benzphetamine	Benzphetamine may decrease the antihypertensive activities of Ramipril.
Ritodrine	Ritodrine may decrease the antihypertensive activities of Ramipril.
Terbutaline	Terbutaline may decrease the antihypertensive activities of Ramipril.
Bitolterol	Bitolterol may decrease the antihypertensive activities of Ramipril.
Almotriptan	Almotriptan may decrease the antihypertensive activities of Ramipril.
Diethylpropion	Diethylpropion may decrease the antihypertensive activities of Ramipril.
Salmeterol	Salmeterol may decrease the antihypertensive activities of Ramipril.
Naratriptan	Naratriptan may decrease the antihypertensive activities of Ramipril.
Rizatriptan	Rizatriptan may decrease the antihypertensive activities of Ramipril.
Formoterol	Formoterol may decrease the antihypertensive activities of Ramipril.
Dopamine	Dopamine may decrease the antihypertensive activities of Ramipril.
Frovatriptan	Frovatriptan may decrease the antihypertensive activities of Ramipril.
Albuterol	Salbutamol may decrease the antihypertensive activities of Ramipril.
Methoxyflurane	Methoxyflurane may decrease the antihypertensive activities of Ramipril.
Ergoloid mesylate	Ergoloid mesylate may decrease the antihypertensive activities of Ramipril.
Isoprenaline	Isoprenaline may decrease the antihypertensive activities of Ramipril.
Arbutamine	Arbutamine may decrease the antihypertensive activities of Ramipril.
Dutasteride	Dutasteride may decrease the antihypertensive activities of Ramipril.
Nefazodone	Nefazodone may decrease the antihypertensive activities of Ramipril.
Pergolide	Pergolide may decrease the antihypertensive activities of Ramipril.
Finasteride	Finasteride may decrease the antihypertensive activities of Ramipril.
Ergometrine	Ergometrine may decrease the antihypertensive activities of Ramipril.
Lisdexamfetamine	Lisdexamfetamine may decrease the antihypertensive activities of Ramipril.
Paliperidone	Paliperidone may decrease the antihypertensive activities of Ramipril.
Arformoterol	Arformoterol may decrease the antihypertensive activities of Ramipril.
Pirbuterol	Pirbuterol may decrease the antihypertensive activities of Ramipril.
Ephedra sinica root	Ephedra sinica root may decrease the antihypertensive activities of Ramipril.
Mephentermine	Mephentermine may decrease the antihypertensive activities of Ramipril.
Procaterol	Procaterol may decrease the antihypertensive activities of Ramipril.
Yohimbine	Yohimbine may decrease the antihypertensive activities of Ramipril.
Clenbuterol	Clenbuterol may decrease the antihypertensive activities of Ramipril.
MMDA	MMDA may decrease the antihypertensive activities of Ramipril.
Midomafetamine	Midomafetamine may decrease the antihypertensive activities of Ramipril.
2,5-Dimethoxy-4-ethylamphetamine	2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Ramipril.
4-Methoxyamphetamine	4-Methoxyamphetamine may decrease the antihypertensive activities of Ramipril.
4-Bromo-2,5-dimethoxyamphetamine	4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Ramipril.
Tenamfetamine	Tenamfetamine may decrease the antihypertensive activities of Ramipril.
Chlorphentermine	Chlorphentermine may decrease the antihypertensive activities of Ramipril.
Dextroamphetamine	Dextroamphetamine may decrease the antihypertensive activities of Ramipril.
Metamfetamine	Metamfetamine may decrease the antihypertensive activities of Ramipril.
Phendimetrazine	Phendimetrazine may decrease the antihypertensive activities of Ramipril.
Periciazine	Periciazine may decrease the antihypertensive activities of Ramipril.
Acepromazine	Acepromazine may decrease the antihypertensive activities of Ramipril.
Thioproperazine	Thioproperazine may decrease the antihypertensive activities of Ramipril.
Zuclopenthixol	Zuclopenthixol may decrease the antihypertensive activities of Ramipril.
Epicaptopril	Epicaptopril may decrease the antihypertensive activities of Ramipril.
1-benzylimidazole	1-benzylimidazole may decrease the antihypertensive activities of Ramipril.
Lysergic acid diethylamide	Lysergic acid diethylamide may decrease the antihypertensive activities of Ramipril.
Amineptine	Amineptine may decrease the antihypertensive activities of Ramipril.
Dronedarone	Dronedarone may decrease the antihypertensive activities of Ramipril.
Flibanserin	Flibanserin may decrease the antihypertensive activities of Ramipril.
Iloperidone	Iloperidone may decrease the antihypertensive activities of Ramipril.
Indacaterol	Indacaterol may decrease the antihypertensive activities of Ramipril.

Target Protein

Angiotensin-converting enzyme ACE

B1 bradykinin receptor BDKRB1

Referensi & Sumber

Synthesis reference: Edward Wilson, Martin Beasley, "Stabilized ramipril compositions and methods of making." U.S. Patent US20060134213, issued June 22, 2006.

Artikel (PubMed)

PMID: 9510492
Cacciapuoti F, Capasso A, Mirra G, De Nicola A, Minicucci F, Gentile S: Prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril in comparison with calcium-channel antagonist, felodipine. Int J Cardiol. 1998 Jan 31;63(2):175-8.
PMID: 10485736
Kleinert S: HOPE for cardiovascular disease prevention with ACE-inhibitor ramipril. Heart Outcomes Prevention Evaluation. Lancet. 1999 Sep 4;354(9181):841.
PMID: 23747952
Douros A, Kauffmann W, Bronder E, Klimpel A, Garbe E, Kreutz R: Ramipril-induced liver injury: case report and review of the literature. Am J Hypertens. 2013 Sep;26(9):1070-5. doi: 10.1093/ajh/hpt090. Epub 2013 Jun 8.
PMID: 8137599
Meisel S, Shamiss A, Rosenthal T: Clinical pharmacokinetics of ramipril. Clin Pharmacokinet. 1994 Jan;26(1):7-15. doi: 10.2165/00003088-199426010-00002.

Textbook

ISBN: 978-1-25-958473-2
Hilal-Dandan R (2018). 26. In Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education.

Link

FDA Approved Products: Altace (ramipril) oral capsules

Contoh Produk & Brand

Produk: 417 • International brands: 11

Produk

Ach-ramipril

Capsule • 1.25 mg • Oral • Canada • Generic • Approved
Ach-ramipril

Capsule • 2.5 mg • Oral • Canada • Generic • Approved
Ach-ramipril

Capsule • 5 mg • Oral • Canada • Generic • Approved
Ach-ramipril

Capsule • 10 mg • Oral • Canada • Generic • Approved
Ach-ramipril

Capsule • 15 mg • Oral • Canada • Generic • Approved
Act Ramipril

Capsule • 1.25 mg • Oral • Canada • Approved
Act Ramipril

Capsule • 2.5 mg • Oral • Canada • Approved
Act Ramipril

Capsule • 5 mg • Oral • Canada • Approved

Menampilkan 8 dari 417 produk.

International Brands

Acovil — Sanofi-Aventis (Spain)
Carasel — Almirall (Spain)
Cardace — Sanofi-Aventis (Finland), Aventis (India), Aventis (Indonesia)
Delix — Aventis (Germany, Turkey),
Hypren — AstraZeneca (Austria)
Lostapres — Temis (Argentina)
Pramace — Astra (Ireland), AstraZeneca (Sweden)
Quark — Polifarma (Italy)
Triatec — Sanofi-Aventis (Brazil, Chili, Denmark, France, Greece, Indonesia, Italy,Norway, Portugal, Sweden, Switzerland)
Tritace — Sanofi-Aventis (Argentina, Australia, Austria, Belgium, Czech Republic, Hong Kong, Hungary, Ireland, Israel, Malaysia, Mexico, Netherlands, Poland, Singapor, Thailand, United Kingdom), Aventis (New Zealand, Philippines, South Africa)

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.