Barnidipine
Barnidipine Uses, Dosage, Side Effects, Food Interaction and all others data.
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 and selectivity against cardiovascular L-type calcium channels . 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 . 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 .
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 . 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 . It also demonstrated clinical efficacy which is similar to that of atenolol, enalapril and hydrochlorothiazide .
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 .
| Trade Name | Barnidipine |
| Generic | Barnidipine |
| Barnidipine Other Names | Barnidipine, Barnidipino, Mepirodipine |
| Type | |
| Formula | C27H29N3O6 |
| Weight | Average: 491.544 Monoisotopic: 491.205635666 |
| Protein binding | In vitro binding of barnidipine with plasma proteins was between 92.4 and 98.9%, and was mainly with albumin . Barnidipine binds at the rate of 26-32% to human erythrocytes. In addition to serum albumin, barnidipine also binds to α1 acid glycoprotein and high density lipoproteins. To a much lesser extent, binding to γ-globulin takes place . |
| Groups | Experimental |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Barnidipine is a calcium channel blocker used to treat various forms of hypertension.
Indicated for the treatment of mild to moderate essential hypertension and management of chronic stable angina.
Barnidipine is also used to associated treatment for these conditions: Essential Hypertension ( Mild to Moderate), Hypertension Arterial, Renovascular Hypertension, Renal parenchymal hypertension
How Barnidipine works
Barnidipine is a lipophilic 1,4-dihydropyridine calcium antagonist that is characterized by a slow onset of action and a strong and long-lasting binding to the L-type calcium channels . It displays high affinity for the channels expressed in the smooth muscle cells in the vascular wall. Its main mechanism of action arises from the reduction of peripheral vascular resistance secondary to its vasodilatory actions.
Calcium ion influx via L-subtype ‘voltage-operated’ channels in the excitable membranes of the smooth muscle cells promotes the formation of calcium-dependent formation of cross-bridges between myosin and actin which are the two major contractile proteins that drive contraction. By blocking the L-type 'voltage-dependent' calcium channels, barnidipine selectively blocks the calcium ion influx in the smooth muscle cells and inhibits the activation of contractile proteins . It is suggested that barnidipine displays a high affinity to the inactivated state of the channel . Like other dihydropyridine calcium antagonists, barnidipine is predicted to interact with the alpha 1-C subunit of the L-type calcium channels. Alpha 1-C subunit of the channel is predicted to reside within the bilayer or channel pore at a location closer to the extracellular rather than the intracellular face of the membrane [A31569, A19705]. Its lipophilicity is likely a reason why barnidipine displays a slow onset and long duration of action. Being a highly lipophilic molecule with an octanol/water partition coefficient of 2000, barnidipine is expected to accumulate in the cell membrane and consequently, gains access to its target receptor in a slow manner .
Toxicity
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 . Oral LD50 in rat and mouse are 105mg/kg and 108mg/kg, respectively .
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) .
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 .
Volume of Distribution
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 .
Elimination Route
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 . 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 . 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 .
Half Life
In a two-compartment analytical model, the median terminal elimination half life of barnidipine was 20 hours after repeated administration .
Elimination Route
Barnidipine and its metabolites are metabolized into feces (60%), urine (40%) and breath (1%) . 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) .
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