Population pharmacokinetics of omeprazole in obese and normal-weight adults.

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.