Nisoldipine coat-core. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of ischaemic heart disease.

Synopsis Nisoldipine coat-core is an extended-release once-daily formulation of a dihydropyridine calcium antagonist effective in the treatment of chronic stable angina pectoris. With immediate-re lease formulations of nisoldipine, plasma drug concentrations that produce therapeutic effects result rapidly, but are not sustained and do not maintain the effects throughout a 12- hour dosage interval. In contrast, with nisoldipine coat-core, a gradual increase in plasma nisoldipine concentrations occurs over 12 hours and therapeutic concentrations are then maintained for the duration of a 24- hour dosage interval. In dosages of 10 to 60mg once daily, nisoldipine coat-core controls symptoms of angina and improves exercise-induced signs of ischaemia in patients with stable angina. Compared with placebo, daily nisoldipine coat-core doses of≥ 20mg provide statistically significant increases in total exercise time and time to produce angina and a trend towards an increase in the time to produce 1mm ST segment depression, in exercise tests conducted≈- 23 hours postdose. When administered in 20 and 40mg daily doses, nisoldipine coat-core produces improvements in exercise test parameters that are similar to those seen with amlodipine 5 or 10 mg/day or regular-release or sustained-release (SR) diltiazem 240 mg/day. The frequency of daily angina attacks and consumption of short-acting nitrates are also reduced by nisoldipine to a similar extent to that observed with these other agents. After longer term (1 year) administration of 10 to 60mg daily, improvements in exercise test parameters are maintained, with equivalent anti-ischaemic efficacy seen in patients receiving nisoldipine coat-core alone or with background nitrate or β-blocker therapy. Adverse events associated with nisoldipine coat-core are typical of the dihydropyridine class of calcium 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 Therapy II) study, where only 1 death occurred with nisoldipine compared with 7 in the placebo group. Nisoldipine should not be taken during phenytoin therapy. In addition, grapefruit juice should be avoided during nisoldipine therapy and nisoldipine should not be taken concurrently with high-fat meals. Thus, the coat-core formulation of nisoldipine appears to have overcome the limitations of the shorter duration of action of immediate-release nisoldipine. Nisoldipine coat-core is well tolerated and once-daily administration produces a long duration of effective anti-ischaemic relief in patients with chronic stable angina pectoris.