Abstract: Objective To study and evaluate the efficacy of penicillamine tablets against Wilson's disease based on a physiological pharmacokinetic model. Methods A physiologically based pharmacokinetic (PBPK) model of penicillamine was established using software and validated with data collected from literature. Plasma concentration-time curves in the corresponding tissues and organs were calculated. The efficacy was evaluated based on the plasma concentration-time curves in related organs via appropriate parameters. Determinants of efficacy were also identified. Results For the single oral administration of 250 mg of penicillamine tablets, the maxiumen concentrations (C_max) were 3.172 and 3.050 μg·mL^-1 respectively based on the model and literature, and the corresponding average areas under the curve (AUC_{0-24 h}) were 22.928 and 23.549 μg·h·mL^-1 respectively. The determining factor (r² value) between the results of calculation by the model and actual measurement in literature was 0.947, suggesting that there was no difference between the two results. Further calculation showed that the cmax of the brain, muscle, liver, heart, brain and kidney was 4.962, 4,783, 2.385, 1.641 and 0.616 μg·mL^-1 respectively, while the AUC_0-24h was 35.863, 32.518, 17.240, 12.003 and 4.450 μg·h·mL^-1 within 24 hours of oral administration. Conclusion There is difference in the distribution of penicillamine tablets in various organs after oral administration. The administration scheme has to be designed and optimized according to the purpose of treatment. Dosage forms that are more likely to exist in the liquid state in the jejunum should be recommended since they can improve the efficacy. The approach established in this study can be used to evaluate the efficacy of penicillamine tablets in the human body and investigate the determinants of efficacy.

Key words: penicillamine tablets, efficacy evaluation, PBPK model, Wilson's disease