Comparison of the Bayesian approach and a limited sampling model for the estimation of AUC and C-max: a computer simulation analysis

Objectives: To compare two limited sampling methods (Bayesian and the limit ed sampling model) for the estimation of AUC and C-max following a single o ral dose of a hypothetical drug. Methods: The plasma concentration vs time data sets for 50 subjects using a linear one- or two-compartment pharmacoki netic model were generated by simulation. The limited sampling model (LSM) was developed using samples from 10 subjects using one or two time points. The simulated plasma concentrations were also used for Bayesian evaluation. Bayesian analysis was performed on Non-Mem and mean pharmacokinetic parame ters used for simulation were assumed as population pharmacokinetic paramet ers. In addition a test drug was also used to compare the predicted AUC and C-max for the two approaches. Results: Both methods were validated in 40 s ubjects for the hypothetical drug and in 12 subjects for the test drug. Bot h methods provided good estimates of AUC and C-max. Conclusion: The results indicate that the LSM is similar to the Bayesian method and may be used in lieu of the Bayesian approach in estimating AUC and C-max, using one or tw o samples in clinical settings without detailed pharmacokinetic studies.