Concentration-effect relationships and implications for trough-to-peak ratio

The guidelines on trough-to-peak ratio identified an index of the duration of action of an antihypertensive drug (relative to its dosage interval) to prevent the use of inappropriately large doses of drug simply to extend the apparent duration of action. In some instances, however, trough-to-peak ratio may be dose-dependent and this analysis examines the contribution that the underlying concentration-antihypertensive effect relationship makes to the dose dependency of trough-to-peak ratio. Where this concentration-effect relationship is essentially linear the trough-to-peak ratio is almost invariably dose-independent. In contrast, where the relationship is identified as being of a sigmoid-Emax type the trough-to-peak ratio is likely to be dose-dependent. The nature of the concentration-effect relationship also influences the duration of action beyond the dosage interval whereby “linear” drugs are superior to “Emax” drugs by virtue of the greater persistence of the antihypertensive effect.