NISOLDIPINE COAT-CORE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND CLINICAL EFFICACY IN THE MANAGEMENT OF ISCHEMIC-HEART-DISEASE

Nisoldipine coat-core is an extended-release once-daily formulation of a dihydropyridine calcium antagonist effective in the treatment of ch ronic stable angina pectoris. With immediate-release formulations of n isoldipine, plasma drug concentrations that produce therapeutic effect s result rapidly, but are not sustained and do not maintain the effect s throughout a 12-hour dosage interval. In contrast, with nisoldipine coat-core, a gradual increase in plasma nisoldipine concentrations occ urs over 12 hours and therapeutic concentrations are then maintained f or the duration of a 24-hour dosage interval. In dosages of 10 to 60mg once daily, nisoldipine cent-core controls symptoms of angina and imp roves exercise-induced signs of ischaemia in patients with stable angi na. Compared with placebo, daily nisoldipine coat-core doses of greate r than or equal to 20mg provide statistically significant increases in total exercise time and lime to produce angina and a trend towards an increase in the time to produce 1mm ST segment depression, in exercis e tests conducted approximate to 23 hours postdose. When administered in 20 and 40mg daily noses, nisoldipine coat-core produces improvement s in exercise test parameters that are similar to those seen with amlo dipine 5 or 10 mg/day or regular-release or sustained-release (SR) dil tiazem 240 mg/day. The frequency of daily angina attacks and consumpti on of short-acting nitrates are also reduced by nisoldipine to a simil ar extent to that observed with these other agents. After longer term (1 year) administration of 10 to 60mg daily, improvements Dt exercise test parameters are maintained with equivalent anti-ischaemic efficacy seen in patients receiving nisoldipine coat-core alone or with backgr ound nitrate or beta-blocker therapy. Adverse events associated with n isoldipine coat-core are typical of the dihydropyridine class of calci um antagonists, with peripheral oedema and headache being most common. Nisoldipine coat-core appears to be associated with fewer deaths than placebo, notably in the DEFIANT-II (Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therap y II) study, where only 1 death occurred with nisoldipine compared wit h 7 in the placebo group. Nisoldipine should not be taken during pheny toin therapy. In addition, grapefruit juice should be avoided during n isoldipine ther npy and nisoldipine should not be taken concurrently w ith high-fat meals. Thus, the coat-core formulation of nisoldipine app ears to have overcome the limitations of the shorter duration of actio n of immediate-release nisoldipine. Nisoldipine coat-core is well tole rated and once-daily administration produces a long duration of effect ive anti-ischaemic relief in patients with chronic stable angina pecto ris.