Peringatan Keamanan

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction L1131. Oral LD50 in rat and mouse are 105mg/kg and 108mg/kg, respectively MSDS.

In general, the clinical symptoms from overdose of calcium antagonists appear within 30 to 60 minutes of after administration of a dose five to ten times higher than the therapeutic dose. Possible symptoms that may develop include hypotension, electrophysiological effects (sinus bradycardia, prolonged AV conduction, second and third degree AV block, tachycardia), effects on the central nervous system (drowsiness, confusion and, rarely, convulsions), gastrointestinal symptoms (nausea and vomiting) and metabolic effects (hyperglycaemia) L1131.

In the case of intoxication, symptomatic treatment and continuous ECG monitoring in the clinical setting are recommended. In the case of overdose, gastric lavage is strongly recommended. An intravenous (dosage 0.2 ml/kg body weight) injection of calcium (preferably 10 ml of a calcium chloride solution of 10%) should be given over a period of 5 minutes, up to a total dose of 10 ml 10%. Contractility of the myocardium, sinus rhythm and atrioventricular conduction will thus be improved. The treatment can be repeated every 15 to 20 minutes (up to a total of 4 doses) based on the patient’s response. Calcium levels should be checked L1131.

Barnidipine

DB09227

small molecule experimental

Deskripsi

Barnidipine is a long-acting novel calcium antagonist that belongs to the dihydropyridine (DHP) group of calcium channel blockers. Used in the treatment of hypertension, barnidipine displays high affinity for the calcium channels of the smooth muscle cells in the vascular wall L1131 and selectivity against cardiovascular L-type calcium channels A7842. Barnidipine contains two chiral centres thus can have four possible enantiomers. The active component is composed of a single optical isomer (*3'S, 4S* configuration), which is the most potent and longest-acting of the four enantiomers A31567. Compared to several other calcium antagonists which are racemates, the barnidipine compound consisting of a single enantiomer may offer a high degree of pharmacological selectivity A31567.

According to a dose-ranging, multicentre, placebo-controlled, double-blind study in patients with mild to moderate hypertension, the antihypertensive response from barnidipine treatment was maintained after a 1-year and 2-year follow-up period in 91% of the patients who had an initial response to the drug A7842. In two European multicentre randomized, double-blind trials, barnidipine was shown to possess equivalent antihypertensive efficacy to amlodipine and nitrendipine, but produced fewer class-specific side-effects A31568. It also demonstrated clinical efficacy which is similar to that of atenolol, enalapril and hydrochlorothiazide A7842.

It is available in modified-release oral tablets under the brand name Vasexten to be taken once daily in the morning. Barnidipine has a gradual onset of action and is shown to be well tolerated in patients. It does not produce reflex tachycardia A7842.

Struktur Molekul 2D

Berat 491.544
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) In a two-compartment analytical model, the median terminal elimination half life of barnidipine was 20 hours after repeated administration [L1131].
Volume Distribusi After administration of single oral doses of radiolabelled barnidipine in rats, levels of radioactivity were found to be higher in the kidney, liver and gastrointestinal tract than in plasma, whereas the brain showed the lowest level of radioactivity. The drug was also detectable in the breast milk [A7842].
Klirens (Clearance) -

Absorpsi

Following a single, modified-release dose of 10mg barnidipine, the peak plasma concentration was approximately 0.48 µg/L and the area under the curve (AUC) was 2.85 µg/Lxh A7842. The peak plasma concentrations are reached within 5 to 6 hours after oral administration of 20mg barnidipine. While the plasma concentrations of the drug may vary between individuals, the absolute bioavailability of the barnidipine is approximately 1.1% due to extensive first-pass hepatic metabolism L1131. After repeated administration of 20mg barnidipine to healthy individuals, the concomitant intake of food did not have a statistically significant effect on the AUC, Cmax or half-life of the drug L1131.

Metabolisme

Barnidipine is expected to undergo hepatic metabolism. The primary metabolism of barnidipine involves the oxidation of the 1,4-dihydropyridine ring and hydrolysis of the methyl ester. Secondary metabolism involves N-debenzylization of the side chain, hydrolysis of the N-benzylpyrrolidine ester, and reduction of the nitro group A31566. Both the primary and secondary metabolic pathways are mediated by the CYP3A isoenzyme family and the metabolites formed are pharmacologically inactive A7842, L1131.

Rute Eliminasi

Barnidipine and its metabolites are metabolized into feces (60%), urine (40%) and breath (1%) L1131. Following a single dose administration of barnidipine ranging from 5 to 20mg in healthy volunteers, urinary excretion of unchanged drug was negligible (?0.003% of an administered dose) A7842.

Interaksi Obat

1420 Data
Duloxetine The risk or severity of orthostatic hypotension and syncope can be increased when Barnidipine is combined with Duloxetine.
Levodopa The risk or severity of hypotension and orthostatic hypotension can be increased when Barnidipine is combined with Levodopa.
Risperidone Barnidipine may increase the hypotensive activities of Risperidone.
Ceritinib Barnidipine may increase the bradycardic activities of Ceritinib.
Ruxolitinib Ruxolitinib may increase the bradycardic activities of Barnidipine.
Brexpiprazole The metabolism of Brexpiprazole can be decreased when combined with Barnidipine.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Barnidipine.
Everolimus The metabolism of Everolimus can be decreased when combined with Barnidipine.
Flibanserin The metabolism of Flibanserin can be decreased when combined with Barnidipine.
Ibrutinib The metabolism of Ibrutinib can be decreased when combined with Barnidipine.
Ivabradine The metabolism of Ivabradine can be decreased when combined with Barnidipine.
Ivacaftor The metabolism of Ivacaftor can be decreased when combined with Barnidipine.
Lurasidone The metabolism of Lurasidone can be decreased when combined with Barnidipine.
Naloxegol The metabolism of Naloxegol can be decreased when combined with Barnidipine.
Olaparib The metabolism of Olaparib can be decreased when combined with Barnidipine.
Ranolazine The metabolism of Ranolazine can be decreased when combined with Barnidipine.
Sonidegib The metabolism of Sonidegib can be decreased when combined with Barnidipine.
Avanafil The metabolism of Avanafil can be decreased when combined with Barnidipine.
Eplerenone The metabolism of Eplerenone can be decreased when combined with Barnidipine.
Cilostazol The metabolism of Cilostazol can be decreased when combined with Barnidipine.
Colchicine The metabolism of Colchicine can be decreased when combined with Barnidipine.
Fentanyl The metabolism of Fentanyl can be decreased when combined with Barnidipine.
Iloperidone The metabolism of Iloperidone can be decreased when combined with Barnidipine.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Barnidipine.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Barnidipine.
Vardenafil The metabolism of Vardenafil can be decreased when combined with Barnidipine.
Eszopiclone The metabolism of Eszopiclone can be decreased when combined with Barnidipine.
Zopiclone The metabolism of Zopiclone can be decreased when combined with Barnidipine.
Lovastatin The metabolism of Lovastatin can be decreased when combined with Barnidipine.
Cimetidine The serum concentration of Barnidipine can be increased when it is combined with Cimetidine.
Clopidogrel The therapeutic efficacy of Clopidogrel can be decreased when used in combination with Barnidipine.
Melatonin The therapeutic efficacy of Barnidipine can be decreased when used in combination with Melatonin.
Nafcillin The therapeutic efficacy of Barnidipine can be decreased when used in combination with Nafcillin.
Nitroprusside Barnidipine may increase the hypotensive activities of Nitroprusside.
Dantrolene The risk or severity of hyperkalemia can be increased when Dantrolene is combined with Barnidipine.
Lithium citrate The risk or severity of adverse effects can be increased when Barnidipine is combined with Lithium citrate.
Lithium carbonate The risk or severity of adverse effects can be increased when Barnidipine is combined with Lithium carbonate.
Lithium hydroxide The risk or severity of adverse effects can be increased when Barnidipine is combined with Lithium hydroxide.
Alfuzosin The metabolism of Alfuzosin can be decreased when combined with Barnidipine.
Alprazolam The metabolism of Alprazolam can be decreased when combined with Barnidipine.
Warfarin The serum concentration of Warfarin can be increased when it is combined with Barnidipine.
Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Barnidipine.
(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Barnidipine.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be increased when it is combined with Barnidipine.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Barnidipine.
(S)-Warfarin The serum concentration of (S)-Warfarin can be increased when it is combined with Barnidipine.
Midazolam The serum concentration of Midazolam can be increased when it is combined with Barnidipine.
Tacrolimus The serum concentration of Tacrolimus can be increased when it is combined with Barnidipine.
Atorvastatin The metabolism of Atorvastatin can be decreased when combined with Barnidipine.
Ibutilide Ibutilide may increase the arrhythmogenic activities of Barnidipine.
Hyoscyamine Hyoscyamine may increase the arrhythmogenic activities of Barnidipine.
Atropine Atropine may increase the arrhythmogenic activities of Barnidipine.
Adenosine Adenosine may increase the arrhythmogenic activities of Barnidipine.
Moricizine Moricizine may increase the arrhythmogenic activities of Barnidipine.
Procainamide Procainamide may increase the arrhythmogenic activities of Barnidipine.
Tocainide Tocainide may increase the arrhythmogenic activities of Barnidipine.
Flecainide Flecainide may increase the arrhythmogenic activities of Barnidipine.
Encainide Encainide may increase the arrhythmogenic activities of Barnidipine.
Ajmaline Ajmaline may increase the arrhythmogenic activities of Barnidipine.
Aprindine Aprindine may increase the arrhythmogenic activities of Barnidipine.
Azimilide Azimilide may increase the arrhythmogenic activities of Barnidipine.
Tedisamil Tedisamil may increase the arrhythmogenic activities of Barnidipine.
Vernakalant Vernakalant may increase the arrhythmogenic activities of Barnidipine.
Cariporide Cariporide may increase the arrhythmogenic activities of Barnidipine.
Xylometazoline Xylometazoline may increase the arrhythmogenic activities of Barnidipine.
Sparteine Sparteine may increase the arrhythmogenic activities of Barnidipine.
Fasudil Fasudil may increase the arrhythmogenic activities of Barnidipine.
Melperone Melperone may increase the arrhythmogenic activities of Barnidipine.
Carteolol Barnidipine may increase the arrhythmogenic activities of Carteolol.
Metipranolol Barnidipine may increase the arrhythmogenic activities of Metipranolol.
Tropisetron Barnidipine may increase the arrhythmogenic activities of Tropisetron.
Simendan Barnidipine may increase the arrhythmogenic activities of Simendan.
Spiradoline Barnidipine may increase the arrhythmogenic activities of Spiradoline.
Pilsicainide Barnidipine may increase the arrhythmogenic activities of Pilsicainide.
Cibenzoline Barnidipine may increase the arrhythmogenic activities of Cibenzoline.
Nizofenone Barnidipine may increase the arrhythmogenic activities of Nizofenone.
Prajmaline Barnidipine may increase the arrhythmogenic activities of Prajmaline.
Tiracizine Barnidipine may increase the arrhythmogenic activities of Tiracizine.
Ethacizine Barnidipine may increase the arrhythmogenic activities of Ethacizine.
Lorajmine Barnidipine may increase the arrhythmogenic activities of Lorajmine.
Bunaftine Barnidipine may increase the arrhythmogenic activities of Bunaftine.
Lorcainide Barnidipine may increase the arrhythmogenic activities of Lorcainide.
Hydroquinine Barnidipine may increase the arrhythmogenic activities of Hydroquinine.
Bioallethrin Barnidipine may increase the arrhythmogenic activities of Bioallethrin.
Fosfructose Barnidipine may increase the arrhythmogenic activities of Fosfructose.
Hydroquinidine Barnidipine may increase the arrhythmogenic activities of Hydroquinidine.
SOR-C13 Barnidipine may increase the arrhythmogenic activities of SOR-C13.
Digoxin Digoxin may increase the arrhythmogenic activities of Barnidipine.
Acetyldigitoxin Acetyldigitoxin may increase the arrhythmogenic activities of Barnidipine.
Deslanoside Deslanoside may increase the arrhythmogenic activities of Barnidipine.
Cymarin Barnidipine may increase the arrhythmogenic activities of Cymarin.
Metildigoxin Barnidipine may increase the arrhythmogenic activities of Metildigoxin.
Acetyldigoxin Barnidipine may increase the arrhythmogenic activities of Acetyldigoxin.
Levosimendan Levosimendan may increase the arrhythmogenic activities of Barnidipine.
Trimethadione Trimethadione may increase the arrhythmogenic activities of Barnidipine.
Lamotrigine Lamotrigine may increase the arrhythmogenic activities of Barnidipine.
Cinnarizine Cinnarizine may increase the arrhythmogenic activities of Barnidipine.
Verapamil Verapamil may increase the arrhythmogenic activities of Barnidipine.
Levomenthol Levomenthol may increase the arrhythmogenic activities of Barnidipine.
Zonisamide Zonisamide may increase the arrhythmogenic activities of Barnidipine.

Target Protein

Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C
Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G
Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H

Referensi & Sumber

Artikel (PubMed)
  • PMID: 11434453
    Malhotra HS, Plosker GL: Barnidipine. Drugs. 2001;61(7):989-96; discussion 997-8.
  • PMID: 9058533
    Teramura T, Watanabe T, Higuchi S, Hashimoto K: Metabolism and pharmacokinetics of barnidipine hydrochloride, a calcium channel blocker, in man following oral administration of its sustained release formulation. Xenobiotica. 1997 Feb;27(2):203-16. doi: 10.1080/004982597240695 .
  • PMID: 9660520
    van Zwieten PA: Pharmacological profile of barnidipine: a single optical isomer dihydropyridine calcium antagonist. Blood Press Suppl. 1998;1:5-8.
  • PMID: 9660522
    Spieker C: Efficacy and tolerability of once-daily barnidipine in the clinical management of patients with mild to moderate essential hypertension. Blood Press Suppl. 1998;1:15-21.
  • PMID: 10952695
    Wegener JW, Meyrer H, Rupp J, Nawrath H: Barnidipine block of L-type Ca(2+) channel currents in rat ventricular cardiomyocytes. Br J Pharmacol. 2000 Aug;130(8):2015-23. doi: 10.1038/sj.bjp.0703514.
  • PMID: 7760349
    Kwan YW, Bangalore R, Lakitsh M, Glossmann H, Kass RS: Inhibition of cardiac L-type calcium channels by quaternary amlodipine: implications for pharmacokinetics and access to dihydropyridine binding site. J Mol Cell Cardiol. 1995 Jan;27(1):253-62.
  • PMID: 19416978
    Tikhonov DB, Zhorov BS: Structural model for dihydropyridine binding to L-type calcium channels. J Biol Chem. 2009 Jul 10;284(28):19006-17. doi: 10.1074/jbc.M109.011296. Epub 2009 May 5.

Contoh Produk & Brand

Produk: 0 • International brands: 0
Belum ada data produk/brand untuk obat ini pada database. Jalankan import DrugBank untuk mengisi field produk/brand.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul