Manidipine Other names: Manidipine hydrochloride

Manidipine is a dihydropyridine calcium channel blocker with anti-hypertensive activity and with pharmacodynamic actions which promote renal function.

The main characteristic of manidipine is its prolonged action, demonstrated in vitro and in vivo, due both to its pharmacokinetic properties and to its high affinity for the receptor binding site. In many experimental hypertension models, manidipine was shown to be more efficient and have a more prolonged action than nicardipine and nifedipine.

In addition, manidipine presented vascular selectivity, particularly in the kidneys, increasing renal blood flow, reducing the vascular resistance of the afferent and efferent glomerular capillary vessels, leading consequently to a reduction of intraglomerular pressure.

This property is complemented by its diuretic action, through the inhibition of water and sodium reabsorbtion in the tubules. In experimental pathology trials, manidipine exercised a protective effect over the development of glomerular damage caused by hypertension at only moderate antihypertensive doses. In vitro studies showed that therapeutic concentrations of manidipine can effectively inhibit cellular proliferative response to vascular mitogens (PDGF, endothelin-1),which may represent the pathophysiological basis for renal and vascular damage in hypertensive patients. In hypertensive patients, after one single daily dose, a clinically significant reduction in blood pressure was maintained for 24 hours. This blood pressure reduction caused by the reduction of total peripheral resistance does not lead to a clinically significant increase of cardiac frequency and output during short- or longterm administration.

Manidipine has not been shown to affect glucose metabolism or lipid profile in hypertensive diabetic patients.

After oral administration, maximum plasma concentration is achieved in 2-3.5 hours.

Manidipine undergoes first-pass metabolism.

Binding to plasma proteins is 99%. The medicinal product is widely distributed to the tissues and is extensively metabolised, mainly by the liver.

It is mainly eliminated through faeces (63%) and, to a lesser extent, through urine (31%).

No accumulation is noted after repeated administration. The drug pharmacokinetic is not modified in patients with renal failure.

Absorption of manidipine increases in the presence of food in the gastrointestinal tract.