Use of trough:peak ratio in the assessment of antihypertensive drug therapy.

The trough:peak ratio (TPR) has been used to describe the extent to which an antihypertensive drug achieves adequate blood pressure control over the entire dosing interval. The TPR represents the net fall in blood pressure just before the next dose of medication is taken divided by the maximum reduction in blood pressure. For dihydropyridine calcium antagonists, the TPR is highly dependent upon the pharmacokinetics of the individual compound since the antihypertensive response correlates with the log drug plasma concentration. Accordingly, longer acting formulations exhibit a TPR close to unity with the maximum fall in blood pressure similar to the reduction at the end of the dosing interval. The application of TPR to angiotensin-converting enzyme inhibitors has unmasked a number of methodological problems associated with this approach to evaluating a drug's antihypertensive profile. The TPR has been calculated with and without subtracting responses to placebo with first doses and after several weeks of chronic therapy, and in responders only versus all subjects. Different approaches have also been taken to calculate the TPR, leading to marked variations in values. A review of the existing literature leads to the conclusion that improvements in the standardization of study design and data analysis are needed before TPR can become an accepted measure of 24 h blood pressure control.