Systemic exposure of a drug is generally associated with its pharmacodynamic (PD) effect (e.g., efficacy and toxicity). In this regard, the change in area under the plasma concentration-time curve (AUC) of a drug, representing its systemic exposure, has been mainly considered in evaluation of drug-drug interactions (DDIs). Besides the systemic exposure, the drug concentration in the tissues has emerged as a factor to alter the PD effects. In this review, the status of systemic exposure, and/or tissue exposure changes in DDIs, were discussed based on the recent reports dealing with transporters and/or metabolic enzymes mediating DDIs. Particularly, the tissue concentration in the intestine, liver and kidney were referred to as important factors of PK-based DDIs.
Keywords: drug interaction; pharmacokinetics; systemic exposure; tissue-specific.