Abouir Kenza, Varesio Emmanuel, Déglon Julien, Samer Caroline, Daali Youssef
Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
School of Pharmaceutical Sciences; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.
Basic Clin Pharmacol Toxicol. 2024 Dec;135(6):755-766. doi: 10.1111/bcpt.14095. Epub 2024 Oct 9.
Omeprazole (OME) is a CYP2C19 phenotyping probe, marketed as a racemic (S)/(R) mixture or as an S-enantiomer. Both CYP2C19 and CYP3A4 enzymes mediate (R)-OME hydroxylation to (R)-5-hydroxyomeprazole, while (S)-OME is exclusively hydroxylated via CYP2C19. This study investigates OME and its 5-hydroxymetabolite enantiomers' pharmacokinetics using data from two studies involving healthy volunteers. In Study A, volunteers received OME alone in Session 1, OME combined with voriconazole and fluvoxamine in Session 2 and finally OME with rifampicin in Session 3. In Study B, volunteers received OME alone in Session 1, OME combined with voriconazole in Session 2 and finally OME with fluvoxamine in Session 3. Despite low metabolic ratio values of (S)-OME, detectable modulation of CYP2C19 activity suggests both (R)- and (S)-OME isomers could effectively assess CYP2C19 activity. Further research is needed for precise cut-offs in different phenotype groups.
奥美拉唑（OME）是一种CYP2C19表型探针，以消旋体（S）/（R）混合物或S-对映体形式上市。CYP2C19和CYP3A4酶都介导（R）-OME羟基化为（R）-5-羟基奥美拉唑，而（S）-OME仅通过CYP2C19进行羟基化。本研究利用两项涉及健康志愿者的研究数据，调查了OME及其5-羟基代谢物对映体的药代动力学。在研究A中，志愿者在第1阶段单独接受OME，在第2阶段接受OME与伏立康唑和氟伏沙明联合用药，最后在第3阶段接受OME与利福平联合用药。在研究B中，志愿者在第1阶段单独接受OME，在第2阶段接受OME与伏立康唑联合用药，最后在第3阶段接受OME与氟伏沙明联合用药。尽管（S）-OME的代谢率值较低，但CYP2C19活性的可检测调节表明，（R）-和（S）-OME异构体都可以有效评估CYP2C19活性。不同表型组的精确临界值还需要进一步研究。
