2026 Volume 31 Issue 1 Pages 1-10
This study aimed to propose a novel in silico modeling and simulation approach for toxicokinetic prediction of inhaled materials. Tranilast (TL) was used as a model weakly acidic poorly water-soluble compound. Toxicokinetic profiles of intratracheal TL microparticles (mTL) and nanoparticles (nTL) were predicted using STELLAⓇ software based on input parameters obtained from in vitro experiments and toxicokinetic parameters in rats. The predicted toxicokinetic profiles of intratracheal TL samples were compared with observed profiles in rats. In the model incorporating mucociliary clearance of undissolved particles, precipitation, and the fraction of unionized compound, there was good agreement between the predicted and observed maximum plasma concentrations and areas under the concentration-time curve of intratracheal mTL and nTL with percent errors ranging from –36 to 89%. Poor predictive accuracy in models without consideration of precipitation or the fraction of the unionized compound suggested their impact on the predictive performance of toxicokinetic profiles of intratracheal TL samples. Although further studies are needed to confirm the general applicability of the proposed model, the present approach could provide a useful tool for predicting toxicokinetic profiles of weakly acidic poorly water-soluble compounds in inhalation toxicity testing.
