Rational Drug Delineation: A Global Sensitivity Approach Based on Therapeutic Tolerability to Deviations in Execution

Noncompliance to therapeutic regimen is a real public health problem with tremendous socioeconomic consequences. Instead of direct intervention to patients, which can add extra burden to the already overloaded health system, alternative strategies oriented to drugs’ own properties turns to be more appealing. The aim of this study was establish a rational way to delineate drugs in terms of their “forgiveness”, based on drugs PK/PD properties. A global sensitivity analysis has been performed to identify the most sensitive parameters to dose omissions. A Comparative Drug Forgiveness Index (CDFI), to rank the drugs in terms of their tolerability to non compliance, has been proposed. The index was applied to a number of calcium channel blockers, namely benidipine, nivaldipine, manidipine and felodipine. Using the calculation, benedipine and manidipine showed the best performance among those considered. This result is in accordance with what has been previously reported. The classification method developed here proved to be a powerful quantitative way to delineate drugs in terms of their forgiveness and provides a complementary decision rule for clinical and experimental studies.