当前位置： SCI文献检索 > EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Omeprazole limited sampling strategies to predict area under the concentration-time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping.

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

Abstract：

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 <15%. RESULTS:For CYP2C19, the AUC(OPZ,OBS)/AUC(5OH,OBS) was [mean ± standard deviation (SD)] 2.10 ± 1.63. Five LSS models of AUC(OPZ,PRE)/AUC(5OH,PRE) were generated, but none met the bias or precision criteria. Upon stratification by CYP2C19 genotype and ethnicity, a three-timepoint (at 1, 2, and 4 h) LSS model accurately predicted AUC(OPZ)/AUC(5OH) in Caucasian CYP2C19*1/*1 subjects. For CYP3A, AUC(OPZ,OBS)/AUC(SUL,OBS) (mean ± SD) was 1.79 ± 0.67. All LSS models had unacceptable %MAE, even when stratified by CYP2C19 genotype and ethnicity. CONCLUSIONS:A LSS model to predict AUC(OPZ)/AUC(5OH), and thus CYP2C19 activity, was generated for Caucasian CYP2C19*1/*1 subjects. However, additional model validation is needed prior to general use. LSS models to predict AUC(OPZ)/AUC(SUL), and thus CYP3A activity, were not possible, even upon stratification by CYP2C19 genotype and ethnicity.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Lawson EB,Wu JC,Baldwin RM,Ingelman-Sundberg M,Rosenborg S,Yim DS,Yin OQ,Capparelli EV,Ma JD

doi

10.1007/s00228-011-1136-y

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

407-13

issue

eissn

0031-6970

issn

1432-1041

journal_volume

pub_type

临床试验,杂志文章

在线工具

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