Comparison of the Bayesian approach and a limited sampling model for the estimation of AUC and Cmax: a computer simulation analysis.
OBJECTIVE
To compare two limited sampling methods (Bayesian and the limited sampling model) for the estimation of AUC and Cmax following a single oral dose of a hypothetical drug.


METHODS
The plasma concentration vs time data sets for 50 subjects using a linear one- or two-compartment pharmacokinetic 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 parameters used for simulation were assumed as population pharmacokinetic parameters. In addition a test drug was also used to compare the predicted AUC and Cmax for the two approaches.


RESULTS
Both methods were validated in 40 subjects for the hypothetical drug and in 12 subjects for the test drug. Both methods provided good estimates of AUC and Cmax.


CONCLUSIONS
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 Cmax using one or two samples in clinical settings without detailed pharmacokinetic studies.
Mahmood
I
I
Division of Pharmaceutical Evaluation I, Office of Clinical Pharmacology and Biopharmaceutics, Rockville, MD 20852, USA.
Miller
R
R
D019540:Area Under Curve; D001499:Bayes Theorem; D001774:Blood Chemical Analysis; D003198:Computer Simulation; D006801:Humans; D008962:Models, Theoretical; D010599:Pharmacokinetics; D012494:Sampling Studies