Antihypertensive treatment and trough: peak ratio: general considerations.

AIM

The proposed United States Food and Drug Administration guidelines on the trough: peak ratio were established to define the duration of action of an antihypertensive drug and to prevent the 'apparent' duration of action being extended by inappropriately large doses of drugs. Some studies have indicated that the trough:peak blood pressure response to some antihypertensive drugs is dose-dependent. The aim of the present investigation was to determine the relationship between drug concentration and its effect on the trough:peak ratio, particularly when the antihypertensive effect extends beyond the dose interval.

LINEAR VERSUS SIGMOID RELATIONSHIP BETWEEN BLOOD PRESSURE FALL AND DRUG CONCENTRATION

Where the relationship between effect and concentration is linear the effect of the dose on the trough:peak ratio is minimal. In contrast, where the relationship is sigmoid (Hill equation), the value of the trough:peak blood pressure response is dose-dependent. Drugs with linear relationships between concentration and effect are more likely to sustain a useful antihypertensive response beyond the dose interval than sigmoid drugs. Published studies on the response to missed drug doses support this theoretical differentiation in drug type.

CONCLUSIONS

We conclude that trough:peak blood pressure responses provide a useful arithmetic index of the duration of action of an antihypertensive drug. The nature of the relationship between concentration and effect determines the influence of the dose on the trough:peak ratio and whether the duration of action is extended beyond the dose interval.