Quantitative comparisons of pharmacokinetic drug interactions: a probabilistic approach

An empirically-based approach which permits the comparison of changes in plasma clearance caused by pharmacokinetic drug-interactions is described. The analysis is based on the calculation of simple probability ratios for defined ranges of clearance changes that are caused by one of the interacting drugs. Examples of drugs increasing the clearance of a second drug through enzyme induction and of drugs decreasing the clearance of a second drug through enzyme inhibition are given. Data for each pair of interacting drugs is empirically fitted using either exponential or logarithmic functions. For each type of interaction a family of curves is generated which permits quantitative comparisons of both the extent and frequency of changes in plasma clearance caused by the interaction.