Guidance on Drug Interaction Studies: From the View Point of the Post Marketing.

Abstract

Appropriate information on drug interactions is essential for the medical practitioner when attempting to reduce the number of serious adverse events and to promote the proper use of drugs. Drug interactions should be considered from the perspective both of drugs which cause interactions (interacting drug) and drugs for which effects are affected by the interaction (interacted drug). For interacting drug, it is necessary to evaluate in vivio inhibition potential for each cytochrome P450 isozyme, such as fluvoxamine, a selective serotonin reuptake inhibitor, produce an increase in AUC values of > 150% for CYP1A2 substrate. For interacted drug, it is desirable to estimate the fraction of total plasma clearance for each cytochrome P450 isozyme. In the case of zolpidem, the incomplete dependence of its clearance on CYP3A4 activity has clinical implications for susceptibility to metabolic inhibition. These information for interacting and interacted drugs is useful for concrete management, such as changing the dose and timing of administration.