**Young Hee Choi**

*Review*

College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University\_Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Korea; choiyh@dongguk.edu; Tel.: +82-31-961-5212

Received: 10 April 2020; Accepted: 30 April 2020; Published: 2 May 2020

**Abstract:** 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; tissue-specific; systemic exposure
