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Optimizing delivery systems to tailor pharmacotherapy to cardiovascular circadian events
1Department of Pharmacy Practice, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Insights
Chronotherapeutics, matching drug delivery to circadian rhythms, improve control of hypertension and angina. A novel extended-release verapamil formulation effectively manages early morning blood pressure surges.
Area of Science:
- Cardiovascular pharmacology
- Chronobiology
- Drug delivery systems
Background:
- Hypertension and angina are major cardiovascular risk factors.
- Current extended-release antihypertensives often fail to control early morning blood pressure surges.
- Circadian variations in cardiovascular activity pose challenges for drug efficacy.
Purpose of the Study:
- To discuss the role of chronotherapeutics in managing hypertension and angina.
- To introduce a novel controlled-onset, extended-release (COER-24) delivery system for verapamil hydrochloride.
- To evaluate the efficacy and safety of COER-24 verapamil for cardiovascular conditions.
Main Methods:
- Development of a 24-hour controlled-onset, extended-release (COER-24) delivery system for verapamil hydrochloride.
- Bedtime administration of COER-24 verapamil.
- Assessment of pharmacokinetic and circadian challenges in blood pressure and angina control.
Main Results:
- COER-24 verapamil hydrochloride is the first chronopharmacologic agent approved for hypertension and angina.
- This formulation delivers peak drug concentration during early morning hours when blood pressure rises.
- COER-24 verapamil provides 24-hour blood pressure reduction and a better adverse-effect profile than immediate-release verapamil.
Conclusions:
- Chronotherapeutics, exemplified by COER-24 verapamil, offer improved management of cardiovascular conditions.
- Bedtime administration of COER-24 verapamil effectively addresses early morning blood pressure surges.
- This novel delivery system enhances therapeutic outcomes and tolerability for hypertension and angina patients.
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 anti-hypertensive 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.