Population pharmacokinetics of omeprazole in obese and normal-weight adults. Issue 4 (3rd April 2022)

• Record Type: Journal Article
• Authors: Chen, Kaifeng; Luo, Ping; Yang, Guoping; Zhu, Shaihong; Deng, Chenhui; Ding, Junjie; Lin, Yaqi; Zhu, Liyong; Pei, Qi
• Is Part Of: Expert review of clinical pharmacology. Volume 15:Issue 4(2022)
• Page Start: 461
• Page End: 471
• Publication Date: 2022-04-03
• Subjects: Obesity -- omeprazole -- population pharmacokinetic -- modeling and simulation -- CYP2C19 genotype; Clinical pharmacology -- Periodicals; 615.105
• DOI: 10.1080/17512433.2022.2075343
• Languages: English
• ISSNs: 1751-2433

Abstract

ABSTRACT: 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.