Omeprazole limited sampling strategies to predict area under the concentration–time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping

Purpose To develop a limited sampling strategy (LSS) to predict area under the concentration–time curve (AUC) ratios of omeprazole (AUC OPZ ) to its metabolites 5-hydroxyomeprazole (AUC 5OH ) and omeprazole sulfone (AUC SUL ) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. Methods Data were obtained from 37 (4 women) Caucasian, Chinese, and Korean healthy adults from three published studies. The AUC OPZ , AUC 5OH , and AUC SUL were calculated via noncompartmental analysis. Observed AUC OPZ, OBS /AUC 5OH, OBS and AUC OPZ, OBS /AUC SUL, OBS were determined. Plasma concentrations of omeprazole, 5-hydroxyomeprazole, and omeprazole sulfone at 1, 1.5, 2, 3, 4, 6, and 8 h post-dose were used to generate limited sampling strategy (LSS) models to predict AUC OPZ,PRE /AUC 5OH,PRE and AUC OPZ,PRE/ AUC SUL,PRE . Bias and precision were assessed via percentage mean prediction error (%MPE) and percentage mean absolute error (%MAE), with acceptable limits being