Influence of CYP2C19 Polymorphisms on the Pharmacokinetics of Omeprazole in Elderly Subjects

CYP2C19型 奥美拉唑 药代动力学 置信区间 医学 药理学 CYP3A4型 基因型 胃肠病学 内科学 质子抑制剂泵 细胞色素P450 新陈代谢 化学 生物化学 基因
作者
Joo Young Na,Inseung Jeon,Jangsoo Yoon,Yun Seong Choi,Seo Hyun Yoon,Kyung‐Sang Yu,Jae‐Yong Chung
出处
期刊:Clinical pharmacology in drug development [Wiley]
卷期号:10 (12): 1469-1477 被引量:3
标识
DOI:10.1002/cpdd.966
摘要

Omeprazole blocks the gastric H+ /K+ adenosine triphosphatase, thus inhibiting gastric acid secretion, and is metabolized by cytochrome P450 (CYP) 2C19. Due to the physiological changes in the elderly, there are different pharmacokinetic consequences compared to young people. The aim of this study was to evaluate the pharmacokinetic profiles of omeprazole in 15 elderly participants according to the CYP2C19 genotype. The concentration-time profiles of omeprazole and its metabolites, 5-hydroxy (5-OH) omeprazole and omeprazole sulfone, were similar between the CYP2C19 extensive metabolizer (EM) and intermediate metabolizer groups. In contrast, when comparing the EM group and CYP2C19 poor metabolizer (PM) group, the EM/PM geometric mean ratio (95% confidence interval) of area under the plasma concentration-time curve from time of dosing to the last measurable concentration was 0.52 (0.27-1.01) and that of the IM group was 0.71 (0.32-1.59), indicating that the exposure of omeprazole in the PM group was increased. The exposure of 5-OH omeprazole was significantly decreased in the PM group when compared to the EM group, with an EM/PM geometric mean ratio (95% confidence interval) of 2.20 (1.50-3.22). In conclusion, the tendency of drug exposure according to the CYP2C19 genotype in the elderly and young adults was similar in that the exposure level was highest in the PM group. However, when compared to young adults, the difference between the genotype groups was smaller in the elderly.
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