Drug—Drug Interactions: Examples in USA

Abstract

We introduces three examples for drug interactions from literatures, i.e. terfenadine, grapefruit juice, and cyclosporin A, as well as one from our drug candidate for subarachnoidal hemorrage, tirilazad. It is still difficult to estimate extent of drug-drug interactions related to drug metabolism even by in vitro studies using human liver preparations. It must be necessary to obtain more data on relationships between the in vitro and in vivo study results for estimation of the possibility and extent of the interactions. Recently, drug interactions related to protein binding are not regarded as an important issue in Europe and USA from the reasons: 1) it was shown that historical examples for protein binding drug-drug interactions were caused by inhibition of the metabolism etc., which are other than protein binding, 2) The pharmacokinetic theory also supports the idea. It must be necessary to establish a common principle for this issue between Japan and Europe-USA.