医学
奥美拉唑
药代动力学
CYP2C19型
加药
非金属
人口
质子抑制剂泵
药理学
不利影响
肥胖
内科学
新陈代谢
环境卫生
细胞色素P450
作者
Kaifeng Chen,Ping Luo,Guoping Yang,Shaihong Zhu,Chonghai Deng,Junjie Ding,Yaqi Lin,Liyong Zhu,Qi Pei
标识
DOI:10.1080/17512433.2022.2075343
摘要
Background Obesity is related to many pathophysiological changes that may result in altered drug disposition. Omeprazole is the most common option utilized for acid-related disorders ; however, the pharmacokinetic (PK) and dosing recommendations for the obese patient population are lacking.Methods Data from 40 healthy subjects with normal weights and data from 61 obese subjects were included. The subjects all received a single dose of 20 mg of omeprazole. Nonlinear mixed effects modeling were performed to characterize the effect of obesity on omeprazole PK.Results A one-compartment model with twelve transit absorption compartments and linear elimination described the data best. A lower clearance was observed in the obese patient population than in the normal-weight subjects. Moreover, the CYP2C19 genotype was identified as a significant covariate for clearance.Conclusion Given the potential adverse events related to high exposure to proton pump inhibitors over time, obese patients may require a lower dose of omeprazole for long-term treatment. Further studies in obese individuals into other drugs metabolized by CYP2C19 are warranted, especially those with a narrow therapeutic window.Clinical Trial Registration www.chictr.org.cn identifier is ChiCTR2100046578; www.chinadrugtrials.org.cn identifier is CTR20190175.
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