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 AUCOPZ/AUC5OH-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 AUCOPZ/AUC5OH-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 AUCOPZ/AUC5OH-OPZ after IV. RESULTS: In the correlation between HI and AUCOPZ/AUC5OH-OPZ IV at observed time points, HI3h 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 HI3h 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 HI3h was the best to estimate AUCOPZ/AUC5OH-OPZ (AUCOPZ/AUC5OH-OPZ = 1.37 * HI3h + 0.18 * Age - 7.83, r2 = 0.883, p < 0.001). CONCLUSIONS: This study demonstrated that HI3h after omeprazole IV was able to estimate AUCOPZ/AUC5OH-OPZ, as well as HI3h after PO. Additionally, CYP2C19 activity can be estimated more definitely by using HI after omeprazole IV without intestinal absorption.
RCT Entities:
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 AUCOPZ/AUC5OH-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 AUCOPZ/AUC5OH-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 AUCOPZ/AUC5OH-OPZ after IV. RESULTS: In the correlation between HI and AUCOPZ/AUC5OH-OPZ IV at observed time points, HI3h 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 HI3h 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 HI3h was the best to estimate AUCOPZ/AUC5OH-OPZ (AUCOPZ/AUC5OH-OPZ = 1.37 * HI3h + 0.18 * Age - 7.83, r2 = 0.883, p < 0.001). CONCLUSIONS: This study demonstrated that HI3h after omeprazole IV was able to estimate AUCOPZ/AUC5OH-OPZ, as well as HI3h after PO. Additionally, CYP2C19 activity can be estimated more definitely by using HI after omeprazole IV without intestinal absorption.
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