Estimation of CYP2C19 activity by the omeprazole hydroxylation index at a single point in time after intravenous and oral administration

Objective The purpose of this study was to identify the common time point to achieve hydroxylation index (HI: omeprazole plasma concentration/5-hydroxyomeprazole plasma concentration) reflecting AUC_OPZ/AUC_5OH-OPZ after intravenous (IV) and oral (PO) administration. Methods Twenty young and 28 elderly healthy subjects, including different CYP2C19 genotypes, were enrolled in the study. The young subjects received either 40 mg PO or 20 mg IV omeprazole, whereas the elderly subjects received 10 mg IV. The relation between AUC_OPZ/AUC_5OH-OPZ and HI was determined by Spearman’s rank correlation. Multiple stepwise linear regression analysis was performed to identify the common time point to calculate HI that reflects AUC_OPZ/AUC_5OH-OPZ after IV. Results In the correlation between HI and AUC_OPZ/AUC_5OH-OPZ IV at observed time points, HI_3h showed the highest correlation coefficients (r = 0.894, p < 0.001) in all 48 subjects. The correlation of HI between IV and PO at observed time points showed that HI_3h was highest (r = 0.916, p < 0.001) in 20 young subjects. Additionally, there was no significant difference between HI_3h of IV and that of PO (12.9 ± 15.9 and 12.9 ± 15.1, p = 0.997). The regression equation of HI_3h was the best to estimate AUC_OPZ/AUC_5OH-OPZ (AUC_OPZ/AUC_5OH-OPZ = 1.37 • HI_3h + 0.18 • Age – 7.83, r ² = 0.883, p < 0.001). Conclusions This study demonstrated that HI_3h after omeprazole IV was able to estimate AUC_OPZ/AUC_5OH-OPZ, as well as HI_3h after PO. Additionally, CYP2C19 activity can be estimated more definitely by using HI after omeprazole IV without intestinal absorption.