Physiologically based pharmacokinetic (PBPK) modeling can assist in formulation development. Bicyclol is a novel anti-hepatitis drug. A bilayer osmotic pump table of bicyclol is being developed. PBPK models for bicyclol immediate-release (IR) and controlled-release (CR) tablets in beagle dog, as well as PBPK model for IR tablets in human were constructed. These models incorporated physicochemical properties and in vitro preclinical data. Parameter sensitivity analysis was performed for the effects of solubility and dissolution on pharmacokinetic (PK) parameters. Models were refined by comparing simulated results to experimental measurements. Furthermore, the clinical PK for bicyclol CR tablets was predicted using the in vivo dissolution profile by deconvolution of the mean PK profile of CR tablets in dogs. In summary, the present study described a strategy employing PBPK models to evaluate the effects of formulation factors on PK profiles and predict the performance of bicyclol CR tablets in human.