Intrinsically long-acting agents compared with long-acting chronoformulations

Intrinsically long-acting antihypertensive drugs may be characterized by long elimination half-lives with high trough: peak ratios for decreasing blood pressure. These agents are usually administered once daily in the morning, and at steady-state they provide 24 h blood pressure control, attenuate the early-morning surge in blood pressure, and maintain a normal circadian blood pressure pattern. In comparison, chronoformulations incorporate shorter-acting antihypertensive drugs into a delivery system that is delayed-onset or extended-release, or both. These agents, which are often designed to be given once daily at bedtime, deliver peak drug concentrations that coincide with the early-morning surge in blood pressure. Chronoformulations also provide 24 h blood pressure control. In highly compliant patients, both intrinsically long-acting drugs and chronoformulations are likely to provide comparable blood pressure control. However, in poorly compliant patients who miss doses of medication, intrinsically long-acting drugs are likely to be superior, because they sustain blood pressure control beyond the dosing interval.