A chronotherapeutic approach to the management of hypertension.

Patients with hypertension have a characteristic diurnal pattern of BP variability in a 24-hour period characterized by a high span while awake and active and a low span during sleep and inactivity. Blood pressures in the untreated hypertensive individual decline by approximately 15-20% during sleep compared to average awake values. Early in the morning (assuming a typical day-night activity cycle), BP rises sharply upon awakening when physical and mental activities increase. Antihypertensive therapy has been traditionally dosed in the early morning and in recent years long-acting preparations have been developed that lower BP for up to 24 hours post-dose. However, in many individuals this pattern of drug dosing may be inadequate since pharmacodynamic activity is attenuated at the end of the dosing period when this large rise in BP occurs. Thus, we undertook an assessment of the effects of a new formulation of verapamil dosed nocturnally that has a controlled-onset of delivery (4-6 hours post-dose) and extended release (COER-verapamil). Through ambulatory BP monitoring, evaluation revealed that COER-verapamil produced changes in BP that followed the circadian variability of BP: Lower BP reductions during sleep when ambulatory BP is intrinsically lowest and appropriately larger reductions during the early morning and daytime hours when ambulatory BP values accelerate and plateau to their highest levels. This study demonstrated that it is possible to tailor antihypertensive therapy for to provide a chronotherapeutic regimen for patients with hypertension.