Peringatan Keamanan

In toxicity studies performed in mice, rats, and beagles there was a reported LD50 of 143 mg/kg, 1982 mg/kg and 4000 mg/kg respectively. In repeated dose studies, some of the reported side effects included increased urinary volume, serum lipid, urea nitrogen, liver weight, decreased urinary osmotic pressure and hypertrophy of hepatocytes. Teratogenic studies showed a slight generation of fetal visceral abnormalities. Other toxicity studies showed no effects on fetal development, reproductive ability, genotoxic, allergenic, or oncogenic potential.^L1343

Aranidipine

DB09229

small molecule experimental

Deskripsi

Aranidipine is a novel dihydropyridine derivative that gives rise to two active metabolites (M-1? and M-1?) that exhibit hypotensive activity. It is a calcium antagonist with the formula methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate.^A31895 It was developed by Maruko Seiyaku, introduced by Taiho and launched in Japan in 1997.T88

Struktur Molekul 2D

Berat 388.376

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) The elimination half-life of aranidipine and the M-1 metabolite are 1.1-1.2 hour and 2.7-3.5 hour respectively.[L1343]

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

After administration, aranidipine is rapidly absorbed from the gastrointestinal tract. After absorption, the AUC and Cmax increased linearly in a dose-dependent manner, the Cmax was attained in approximate 3.8-4.8 hours for aranidipine and 4.8-6 hours for the metabolite M-1. The bioavailability of aranidipine in rat, dog, and monkey was about 48%, 41% and 3% respectively.^L1343

Metabolisme

Eight metabolites of aranidipine were found after oral administration. These metabolites were brought by a reduction of the ketone group, oxidation of dihydropyridine ring and de-esterification at the C-3 position.^L1343

Rute Eliminasi

Unchanged aranidipine is found in plasma but not in the urine after 1 hour of administration. Just a small amount of drug was found in the bile. These results indicate that the excretion profile of aranidipine is mainly driven by metabolism and not by excretion. When including the metabolites, 52-56% of the original dose is disposed in the urine, 34-45% in feces and 3-4% in expired air. The excretion in the bile was 59% of the administered dose and 63% of this portion is reabsorbed.^L1343

Interaksi Obat

978 Data

Ceritinib	Aranidipine may increase the bradycardic activities of Ceritinib.
Ivabradine	Aranidipine may increase the bradycardic activities of Ivabradine.
Ruxolitinib	Ruxolitinib may increase the bradycardic activities of Aranidipine.
Cimetidine	The serum concentration of Aranidipine can be increased when it is combined with Cimetidine.
Clopidogrel	The therapeutic efficacy of Clopidogrel can be decreased when used in combination with Aranidipine.
Efavirenz	The serum concentration of Aranidipine can be decreased when it is combined with Efavirenz.
Melatonin	The therapeutic efficacy of Aranidipine can be decreased when used in combination with Melatonin.
Nafcillin	The therapeutic efficacy of Aranidipine can be decreased when used in combination with Nafcillin.
Nitroprusside	Aranidipine may increase the hypotensive activities of Nitroprusside.
Dantrolene	The risk or severity of hyperkalemia can be increased when Dantrolene is combined with Aranidipine.
Lithium citrate	The risk or severity of adverse effects can be increased when Aranidipine is combined with Lithium citrate.
Lithium carbonate	The risk or severity of adverse effects can be increased when Aranidipine is combined with Lithium carbonate.
Lithium hydroxide	The risk or severity of adverse effects can be increased when Aranidipine is combined with Lithium hydroxide.
Boceprevir	The serum concentration of Aranidipine can be increased when it is combined with Boceprevir.
Tocainide	Tocainide may increase the arrhythmogenic activities of Aranidipine.
Aprindine	Aprindine may increase the arrhythmogenic activities of Aranidipine.
Xylometazoline	Xylometazoline may increase the arrhythmogenic activities of Aranidipine.
Sparteine	Sparteine may increase the arrhythmogenic activities of Aranidipine.
Fasudil	Fasudil may increase the arrhythmogenic activities of Aranidipine.
Carteolol	Aranidipine may increase the arrhythmogenic activities of Carteolol.
Metipranolol	Aranidipine may increase the arrhythmogenic activities of Metipranolol.
Tropisetron	Aranidipine may increase the arrhythmogenic activities of Tropisetron.
Spiradoline	Aranidipine may increase the arrhythmogenic activities of Spiradoline.
Tiracizine	Aranidipine may increase the arrhythmogenic activities of Tiracizine.
Ethacizine	Aranidipine may increase the arrhythmogenic activities of Ethacizine.
Hydroquinine	Aranidipine may increase the arrhythmogenic activities of Hydroquinine.
Bioallethrin	Aranidipine may increase the arrhythmogenic activities of Bioallethrin.
Fosfructose	Aranidipine may increase the arrhythmogenic activities of Fosfructose.
Hydroquinidine	Aranidipine may increase the arrhythmogenic activities of Hydroquinidine.
SOR-C13	Aranidipine may increase the arrhythmogenic activities of SOR-C13.
Digoxin	Digoxin may increase the arrhythmogenic activities of Aranidipine.
Acetyldigitoxin	Acetyldigitoxin may increase the arrhythmogenic activities of Aranidipine.
Deslanoside	Deslanoside may increase the arrhythmogenic activities of Aranidipine.
Cymarin	Aranidipine may increase the arrhythmogenic activities of Cymarin.
Metildigoxin	Aranidipine may increase the arrhythmogenic activities of Metildigoxin.
Acetyldigoxin	Aranidipine may increase the arrhythmogenic activities of Acetyldigoxin.
Niguldipine	Aranidipine may increase the arrhythmogenic activities of Niguldipine.
Diltiazem	Diltiazem may increase the arrhythmogenic activities of Aranidipine.
Nimodipine	Nimodipine may increase the arrhythmogenic activities of Aranidipine.
Cinnarizine	Cinnarizine may increase the arrhythmogenic activities of Aranidipine.
Atropine	Atropine may increase the arrhythmogenic activities of Aranidipine.
Adenosine	Adenosine may increase the arrhythmogenic activities of Aranidipine.
Levosimendan	Levosimendan may increase the arrhythmogenic activities of Aranidipine.
Nifedipine	Nifedipine may increase the arrhythmogenic activities of Aranidipine.
Flecainide	Flecainide may increase the arrhythmogenic activities of Aranidipine.
Prenylamine	Prenylamine may increase the arrhythmogenic activities of Aranidipine.
Fluspirilene	Fluspirilene may increase the arrhythmogenic activities of Aranidipine.
Azimilide	Azimilide may increase the arrhythmogenic activities of Aranidipine.
Tedisamil	Tedisamil may increase the arrhythmogenic activities of Aranidipine.
Nilvadipine	Nilvadipine may increase the arrhythmogenic activities of Aranidipine.
Fendiline	Fendiline may increase the arrhythmogenic activities of Aranidipine.
Eperisone	Eperisone may increase the arrhythmogenic activities of Aranidipine.
Melperone	Melperone may increase the arrhythmogenic activities of Aranidipine.
Benidipine	Aranidipine may increase the arrhythmogenic activities of Benidipine.
Simendan	Aranidipine may increase the arrhythmogenic activities of Simendan.
Otilonium	Aranidipine may increase the arrhythmogenic activities of Otilonium.
Nizofenone	Aranidipine may increase the arrhythmogenic activities of Nizofenone.
Bunaftine	Aranidipine may increase the arrhythmogenic activities of Bunaftine.
Lorcainide	Aranidipine may increase the arrhythmogenic activities of Lorcainide.
Penfluridol	Aranidipine may increase the arrhythmogenic activities of Penfluridol.
Dexverapamil	Aranidipine may increase the arrhythmogenic activities of Dexverapamil.
Disopyramide	Disopyramide may increase the arrhythmogenic activities of Aranidipine.
Ibutilide	Ibutilide may increase the arrhythmogenic activities of Aranidipine.
Procainamide	Procainamide may increase the arrhythmogenic activities of Aranidipine.
Bepridil	Bepridil may increase the arrhythmogenic activities of Aranidipine.
Terodiline	Aranidipine may increase the arrhythmogenic activities of Terodiline.
Isradipine	Isradipine may increase the arrhythmogenic activities of Aranidipine.
Trimethadione	Trimethadione may increase the arrhythmogenic activities of Aranidipine.
Amlodipine	Amlodipine may increase the arrhythmogenic activities of Aranidipine.
Lercanidipine	Lercanidipine may increase the arrhythmogenic activities of Aranidipine.
Lamotrigine	Lamotrigine may increase the arrhythmogenic activities of Aranidipine.
Nicardipine	Nicardipine may increase the arrhythmogenic activities of Aranidipine.
Verapamil	Verapamil may increase the arrhythmogenic activities of Aranidipine.
Losartan	Losartan may increase the arrhythmogenic activities of Aranidipine.
Levomenthol	Levomenthol may increase the arrhythmogenic activities of Aranidipine.
Zonisamide	Zonisamide may increase the arrhythmogenic activities of Aranidipine.
Nitrendipine	Nitrendipine may increase the arrhythmogenic activities of Aranidipine.
Perhexiline	Perhexiline may increase the arrhythmogenic activities of Aranidipine.
Nimesulide	Nimesulide may increase the arrhythmogenic activities of Aranidipine.
Cyclandelate	Cyclandelate may increase the arrhythmogenic activities of Aranidipine.
Flunarizine	Flunarizine may increase the arrhythmogenic activities of Aranidipine.
Clevidipine	Clevidipine may increase the arrhythmogenic activities of Aranidipine.
Methsuximide	Methsuximide may increase the arrhythmogenic activities of Aranidipine.
Seletracetam	Seletracetam may increase the arrhythmogenic activities of Aranidipine.
Nylidrin	Nylidrin may increase the arrhythmogenic activities of Aranidipine.
Ziconotide	Ziconotide may increase the arrhythmogenic activities of Aranidipine.
Dotarizine	Dotarizine may increase the arrhythmogenic activities of Aranidipine.
Tranilast	Tranilast may increase the arrhythmogenic activities of Aranidipine.
Agmatine	Agmatine may increase the arrhythmogenic activities of Aranidipine.
Trimebutine	Trimebutine may increase the arrhythmogenic activities of Aranidipine.
Pinaverium	Pinaverium may increase the arrhythmogenic activities of Aranidipine.
Nicorandil	Nicorandil may increase the arrhythmogenic activities of Aranidipine.
Barnidipine	Barnidipine may increase the arrhythmogenic activities of Aranidipine.
Azelnidipine	Aranidipine may increase the arrhythmogenic activities of Azelnidipine.
Cilnidipine	Aranidipine may increase the arrhythmogenic activities of Cilnidipine.
Darodipine	Aranidipine may increase the arrhythmogenic activities of Darodipine.
Efonidipine	Aranidipine may increase the arrhythmogenic activities of Efonidipine.
Lacidipine	Aranidipine may increase the arrhythmogenic activities of Lacidipine.
Manidipine	Aranidipine may increase the arrhythmogenic activities of Manidipine.
Niludipine	Aranidipine may increase the arrhythmogenic activities of Niludipine.

Target Protein

Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C

Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D

Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F

Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S

Alpha adrenergic receptor ADRA1A

Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H

Referensi & Sumber

Artikel (PubMed)

PMID: 9007851
Miyoshi K, Miyake H, Ichihara K, Kamei H, Nagasaka M: Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine. Naunyn Schmiedebergs Arch Pharmacol. 1997 Jan;355(1):119-25.
PMID: 10836731
Nakamura A, Hayashi K, Fujiwara K, Ozawa Y, Honda M, Saruta T: Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection. J Cardiovasc Pharmacol. 2000 Jun;35(6):942-8.
PMID: 10493269
Dhein S, Salameh A, Berkels R, Klaus W: Dual mode of action of dihydropyridine calcium antagonists: a role for nitric oxide. Drugs. 1999 Sep;58(3):397-404.
PMID: 8667194
Miyoshi K, Kanda A, Nozawa Y, Nakano M, Miyake H: Regional vascular effects of MPC-1304, a novel dihydropyridine derivative, in conscious normotensive and spontaneously hypertensive rats. J Pharmacol Exp Ther. 1996 Jun;277(3):1328-36.

Textbook

Allen R. (1988). Annual reports in medicinal chemistry (23rd ed.). Academic press.

Link

Researchgate

Contoh Produk & Brand

Produk: 0 • International brands: 1

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.