Predictable clinical effects in the treatment of hypertension and chronic, stable angina pectoris

Abstract

Drug selection criteria A drug used in the treatment of hypertension and chronic, stable angina pectoris should have simple dosing, predictable efficacy and be well tolerated. Two factors can strongly influence the achievement of these goals: the mechanism of action of the compound and its pharmacokinetic profile. Clinical features Mibefradil, the first member of a new class of calcium antagonists, preferentially blocks transient (T-type) calcium channels. The compound has high bio-availability with a long half-life, and steady-state plasma concentrations are reached within 3–4 days. These pharmacokinetic characteristics are not affected by age, sex, race, body weight or renal function. Treatment with mibefradil results in coronary and peripheral vasodilation, a slight decrease in the heart rate, no negative inotropic effect and no reflex increase in sympathetic activity or neurohormones. There is a strong correlation between the plasma concentration of mibefradil and its clinical effects. Conclusions The results of two large, multicenter, placebocontrolled, randomized trials in hypertension and chronic, stable angina pectoris confirm that the combination of mibefradil's distinct mechanism of action and favorable pharmacokinetic profile achieves the goals of a simple dose schedule, predictable effect and good tolerability. These attributes, in turn, can increase patient compliance, with treatment and physician confidence in ultimately achieving a favorable therapeutic outcome.