Optimizing delivery systems to tailor pharmacotherapy to cardiovascular circadian events

Abstract

The role of chronotherapeutics-agents that match drug delivery to the natural circadian rhythms of the cardiovascular system-in antihypertensive and antianginal therapy is discussed. Hypertension and angina remain two of the most important risk factors for cardiovascular morbidity and mortality. Early-morning increases in blood pressure do not seem to be attenuated by many currently available sustained-release and extended-dosing formulations of antihypertensive agents, such as atenolol, enalapril, sustained-release verapamil, nitrendipine, nifedipine, diltiazem, and long-acting propranolol. A 24-hour controlled-onset, extended-release delivery system (COER-24) for verapamil hydrochloride has recently been developed to address the pharmacokinetic and circadian challenges to controlling blood pressure and angina. COER-24 for verapamil hydrochloride, the first chronopharmacologic agent approved for the treatment of both hypertension and angina, is designed for bedtime administration. It provides the highest concentration of drug in the blood during the early hours of the day, when blood pressure and heart rate are rising rapidly. COER-24 for verapamil hydrochloride has a more favorable adverse-effect profile than is seen with immediate-release verapamil. COER-24 for verapamil hydrochloride provides effective blood pressure reduction for 24 hours and protects against the early-morning increase in blood pressure; the drug has a more favorable adverse-effect profile than immediate-release verapamil.