Nicorandil

Absorption

Following oral administration, nicorandil is well absorbed from the gastrointestinal tract with the oral bioavailability of 75% with the maximum peak plasma concentration (Cmax) reached within 30-60 minutes. The mean Cmax is Cmax then is approximately 300 ng/ml . Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after twice daily dosing (10 or 20mg) .

Toxicity

Common adverse effects include lethargy, back pain, chest pain, infection, feeling of weakness. In the cardiovascular system, hypotension, increased heart rate in higher doses, palpitations, worsened angina pectoris and vasodilation/flush may be observed. Dyspepsia, nausea, and vomiting may occur as gastrointestinal disorders. Headaches may arise from vasodilation. Other common side effects include myalgia, bronchitis, dyspnoea, and respiratory disorder . Nicorandil does not affect fertility of male or female rats, and shows no potential in carcinogenic, mutagenic or genotoxic studies . Oral LD50 values in mouse, rat and dog are 626 mg/kg, 1220 mg/kg and 62.5 mg/kg, respectively .

The Uses of Nicorandil

Nicorandil is a vasodilator used for the prophylaxis and treatment of angina. This medication widens blood vessels thus increasing the blood and oxygen flow to the heart. It is not currently available in the US.
Nicorandil is a nitric oxide donor and ATP-sensitive potassium channel opener. A study showed that Nicorandil is able to protect against stress-induced cell death in dystrophin-deficient cardiomyocytes and also preserve cardiac function in the mdx mouse heart subjected to ischemia and reperfusion injury.

Indications

Indicated for the prevention and treatment of chronic stable angina pectoris and reduction in the risk of acute coronary syndromes.

Background

Nicorandil is an orally efficacious vasodilatory drug and antianginal agent marketed in the UK, Australia, most of Europe, India, Philippines, Japan, South Korea, and Taiwan. It is not an approved drug by FDA. It is a niacinamide derivative that induces vasodilation of arterioles and large coronary arteries by activating potassium channels. It is often used for patients with angina who remain symptomatic despite optimal treatment with other antianginal drugs . Nicorandil is a dual-action potassium channel opener that relaxes vascular smooth muscle through membrane hyperpolarization via increased transmembrane potassium conductance and increased intracellular concentration of cyclic GMP. It is shown to dilate normal and stenotic coronary arteries and reduces both ventricular preload and afterload .

What are the applications of Application

Nicorandil is a small molecule KATP (Kir6) channel opener and NO donor

Pharmacokinetics

Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator . It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow, however the effect of the drug on coronary arteries does not involve the coronary steal phenomenon . Activation of potassium channels lead to hyperpolarization of the smooth muscle cells, followed by arterial dilation and afterload reduction. Nicorandil is shown to increase pooling in the capacitance vessels with a decrease in preload through relaxing the venous vascular system. Overall, improved blood flow and reduced infarct size are achieved through reduction of end-diastolix pressure and decreased extravascular component of vascular resistance . Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris .

Metabolism

Nicorandil undergoes extensive hepatic metabolism . The main biotransformation pathways of nicorandil are denitration, followed by subsequent nicotinamide metabolism. The main pharmacologically inactive denitrated metabolite 2-nicotinamidoethanol can be detected in the urine. The derivatives formed from the nicotinamide metabolism of denitrated products are nicotinuric acid, nicotinamide, N-methylnicotinamide and nicotinic acid .