Effects of obesity on the pharmacology of proton pump inhibitors: current understanding and future implications for patient care and research.

Document Type

Article

Publication Date

1-2023

Identifier

DOI: 10.1080/17425255.2023.2178897

Abstract

INTRODUCTION: In the United States, obesity affects approximately ⅖ adults and ⅕ children, leading to increased risk for comorbidities, like gastroesophageal reflux disease (GERD), treated increasingly with proton pump inhibitors (PPIs). Currently, there are no clinical guidelines to inform PPI dose selection for obesity, with sparse data regarding whether dose augmentation is necessary.

AREAS COVERED: We provide a review of available literature regarding the pharmacokinetics (PK), pharmacodynamics (PD), and/or metabolism of PPIs in children and adults with obesity, as a step toward informing PPI dose selection.

EXPERT OPINION: Published PK data in adults and children are limited to first-generation PPIs and point toward reduced apparent oral drug clearance in obesity, with equipoise regarding obesity impact on drug absorption. Available PD data are sparse, conflicting, and limited to adults. No studies are available to inform the PPI PK→PD relationship in obesity and if/how it differs compared to individuals without obesity. In the absence of data, best practice may be to dose PPIs based on CYP2C19 genotype and lean body weight, so as to avoid systemic overexposure and potential toxicities, while monitoring closely for efficacy.

Journal Title

Expert Opin Drug Metab Toxicol

Volume

19

Issue

1

First Page

1

Last Page

11

MeSH Keywords

Child; Humans; Proton Pump Inhibitors; Gastroesophageal Reflux; Obesity; Patient Care

Keywords

CYP2C19; GERD; obesity; pediatric obesity; proton pump inhibitors; weight-based dosing

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