Background and Objective <p>Obtaining pharmacokinetic curves is crucial for drug dosage selection, and for assessment of efficacy and adverse effects in clinical practice. The aim of this study was to utilize a minimal physiologically-based pharmacokinetic model to predict concentration–time profiles of cinacalcet hydrochloride, a poorly soluble drug, under fasting and fed conditions, and further to establish correlations between in vivo and in vitro dissolution profiles of cinacalcet hydrochloride.</p> Methods <p>The mPBPK model consisted of six tissue compartments, and an additional compartmental absorption and transit model, incorporating the stomach, seven small intestinal compartments, and the large intestine along with Johnson’s equation, was integrated to enable precise calculations of in vivo dissolution.</p> Results <p>External validations for three dosages showed that the average fold error and the absolute average fold error were all within a two-fold error range, indicating the accuracy and reliability of the established model. Subsequently, the model was used to calculate the in vivo dissolution profile and to establish a correlation with the in vitro dissolution profile (<i>R</i>²&#xa0;=&#xa0;0.991 in fasting conditions and <i>R</i>²&#xa0;=&#xa0;0.991 in fed conditions, both in water medium). Notably, under fasting conditions, this correlation exhibited superior performance compared to convolution, deconvolution, and Wagner–Nelson methods. However, under fed conditions, all four methods demonstrated satisfactory correlations.</p> Conclusion <p>The mPBPK model can accurately predict the plasma concentration–time curves under both fasted and fed conditions, and provides a new perspective for establishing in vivo–in vitro correlations of drug products such as incomplete in vivo release, sustained/controlled release, and poor absorption.</p>