Pharmacokinetics (PK) research is crucial in developing new drugs, from searching for seed compounds to conducting clinical trials . In general, the parameters significantly affecting the blood concentration profile of a drug are volume of distribution (Vd), which quantifies the distribution of the drug inside the human body, and total body clearance (CLtot), which shows the drug processing capacity of the entire body . However, these parameters only reveal the drug's exposure to the blood (or plasma). From the viewpoint of the PK/PD concept, more direct information is often obtained from the unbound concentrations in target tissues . Physiologically based pharmacokinetics (PBPK) modeling has been used to predict drug concentration in target tissues. The U.S. Food and Drug Administration (FDA), along with the European Medicines Agency (EMA), announced and released the availability of their guidance documents for the PBPK model . Consequently, when submitting a new drug application (NDA), researchers can use the PBPK model to explain the various PK concerns. Based on survey, over 20 PBPK models of drugs have been submitted to the FDA and/or EMA, 80% of which were accepted by 2018 . The PBPK model has various utilities, including predicting drug concentration-time profile and PK parameters, DDI magnitude, effect on special populations (e.g., pediatrics, elderly, and pregnancy), bioequivalence, and food effect . The PBPK model consists of organ compartments with specific volumes and blood flow rates connected by the circulatory system. Tissue-to-plasma partition coefficient (Kp) is one of the most important parameters in PBPK modeling. It is the ratio of the drug concentration in the tissue to that in plasma, representing the amount of drug transferred to or retained in the tissue. Kp is used in a perfusion-limited model, the limiting process of which is the blood flow to the tissue. Here, Kp divides the drug concentration in a tissue to produce the plasma concentration (also blood concentration using Rb), which returns to the blood system, and differential equations can be used to account for it . The guidelines of drug regulatory authorities suggest distribution studies in animals, such as rats and monkeys (i.e., Kp in animals), as it is difficult to determine the concentration in human tissues 9 .