physiologically-based pharmacokinetic (PBPK) modeling and simulation are often used to predict the ADME (absorption, distribution, metabolism, and excretion) of drugs in human from preclinical species and in vitro-in vivo extrapolation.In addition, PBPK can be used to evaluate the effect of intrinsic (e.g., demography, genetics, physiology) and extrinsic (e.g., drug interactions) factors on the exposure and has been increasingly used in regulatory review to accelerate the decision-making.The applications of PBPK modeling and simulation include but not limited to candidate selection, formulation development, food effect evaluation, prediction of first-in-human dose, and drug interaction potentials.PBPK has been widely used to address important questions and enable decision-making in all drug development processes.