THE CIRCADIAN PATTERN OF BLOOD-PRESSURE - CARDIOVASCULAR RISK AND THERAPEUTIC OPPORTUNITIES

It has been known for many years that humans possess internal time clo cks that regulate multiple physiologic factors (chronobiology). Epidem iologic studies have demonstrated that the peak incidence of many dise ases, including respiratory disease (asthma, allergy), cardiovascular disease (hypotension, angina, myocardial infarction, stroke), as well as several others, tends to occur in a circadian pattern, In particula r, studies utilizing ambulatory blood pressure monitoring have demonst rated that blood pressure has a very definite and reproducible circadi an pattern over a 24-h period, Blood pressure is highest during the da y, lowest during sleep, and then rapidly increases during the period 0 400 h to 1 200 h, Because recent data have demonstrated a possible cau se-effect relationship between increases in blood pressure and angina, effective antihypertensive control in the early morning is desirable, Some once-a-day drugs taken in the morning may lose efficacy in the l ast few hours of the dosing interval, resulting in increases in blood pressure during the early morning period, In an attempt to ensure peak plasma levels during the early morning period, novel, controlled-onse t, extended release-delivery systems have been developed, Studies usin g these delivery systems have demonstrated that, when dosed at night, these formulations provide maximal plasma levels during the period 060 0 h to 1 200 h, when blood pressure is physiologically rising at its g reatest rate. The use of drugs designed to have peak efficacy at certa in desirable times in the circadian pattern is referred to as chronoth erapeutics.