LACK OF PHARMACOKINETIC INTERACTION AS AN EQUIVALENCE PROBLEM

The demonstration that concomitant administration of drug B does not a ffect the pharmacokinetics of drug A can be adequately handled as an e quivalence problem. Administration of drug A alone serves as reference and simultaneous administration of drugs A and B as test situation. T he range of clinically acceptable variation in the pharmacokinetic cha racteristics of drug A defines the equivalence range. This will usuall y correspond to the bioequivalence range accepted for the comparison o f different formulations of drug A. Equivalence, i.e. lack of pharmaco kinetic interaction, is concluded if the 90%-confidence interval for t he ratio (difference) of the expected medians for test and reference i s entirely within the equivalence range. This decision procedure ensur es that the consumer risk of incorrectly concluding ''lack of interact ion'' is limited to 5%. Moreover, the producer risk of incorrectly con cluding ''interaction'' can be controlled by appropriate sample sizes.