Abstract: AIM: To predict the AUC with an example by the limited sampling strategy (LSS)and compare the performance of three approaches for internal validation.METHODS: Twenty healthy subjects received 200 mg tiopronin po.A multi-linear regression analysis of the AUC against the tiopronin concentration was carried out to estimate AUC by LSS.According to the values of rmse and Pe, the regressionmodel was validated by the simulation, Bootstrap method and Jackknife method.RESULTS: The model (AUC_0-48=9.36+1.81C₃+23.28 C₈)was accurately validated by the simulation data.The parameters obtained from the simulation, Bootstrap method and Jackknife method were that Intercept=17.58, 9.33, 9.84;M₁=1.01, 1.76, 1.84;M₂=6.17, 23.14, 21.36;and rmse=3.87, 1.94, 2.23.CONCLUSION: The simulation can evaluate the multi-linear regression model by the estimated AUC, and not by the estimated regression model parameters.The Bootstrap and the Jackknife are appropriate approaches as internal validation of the model.

Key words: tiopronin, limited sampling strategy, simulation, Bootstrap, Jackknife