Vw. Steinijans et al., LACK OF PHARMACOKINETIC INTERACTION AS AN EQUIVALENCE PROBLEM, International journal of clinical pharmacology and therapeutics, 34, 1996, pp. 25-30
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.