Drug Interactions

Abstract Drug interaction is the alteration of drug disposition (i.e. pharmacokinetics) and/or drug effect (i.e. pharmacodynamics) of one drug due to the presence of a second drug. In pharmacokinetic interaction, one drug's elimination rate or enzyme‐mediated metabolism may be inhibited or induced by a second drug. During pharmacodynamic interaction, the net drug effect may be enhanced or diminished or a new side‐effect may appear that was not seen with either drug alone. To assess drug interaction, a randomized complete block design is employed in which all treatments (e.g. each single drug and the combination) are administered to each subject. The order of the treatments is randomly assigned. Disposition and/or effect measures are repeated after each treatment is administered. Using planned contrasts, the interaction is tested by comparing the treatment means for a single drug to that of the combination.