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) to its metabolites 5-hydroxyomeprazole (AUC) and omeprazole sulfone (AUC) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. Methods: Data were obta...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 68; no. 4; pp. 407 - 414 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Apr2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104529953&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104529953 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Apr2012 vid: 68 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104529953 73277848 10.1007/s00228-011-1136-y NLM22009190 104529953 ppf: 407 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Omeprazole limited sampling strategies to predict area under the concentration-time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping. aug: au: Lawson, Eileen Wu, Jerry Baldwin, R. Ingelman-Sundberg, Magnus Rosenborg, Staffan Yim, Dong-Seok Yin, Ophelia Capparelli, Edmund Ma, Joseph affil: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego (UCSD), 9500 Gilman Drive, MC 0714 La Jolla 92093-0714 USA sug: subj: Omeprazole Metabolism Drug Monitoring Methods Omeprazole Pharmacokinetics Genotype Human Secondary Analysis Male Female Descriptive Statistics Measurement Issues and Assessments Phenotype Chromatography, High Pressure Liquid Data Analysis Software Young Adult Adult Multiple Linear Regression Adult: 19-44 years Male Female ab: Purpose: To develop a limited sampling strategy (LSS) to predict area under the concentration-time curve (AUC) ratios of omeprazole (AUC) to its metabolites 5-hydroxyomeprazole (AUC) and omeprazole sulfone (AUC) 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, AUC, and AUC were calculated via noncompartmental analysis. Observed AUC/AUC and AUC/AUC 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/AUC and AUCAUC. 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/AUC was [mean ± standard deviation (SD)] 2.10 ± 1.63. Five LSS models of AUC/AUC 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/AUC in Caucasian CYP2C19*1/*1 subjects. For CYP3A, AUC/AUC (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/AUC, 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/AUC, and thus CYP3A activity, were not possible, even upon stratification by CYP2C19 genotype and ethnicity. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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