Pharmacokinetics of single and repeated oral doses of esomeprazole and gastrin elevation in healthy males and females

Abstract

Objective

Gastrin elevation secondary to proton pump inhibitor (PPI) therapy is well documented. Recent studies have demonstrated a sex-related difference where females on PPIs have significantly higher baseline gastrin levels than males. The aim of the study was to analyse the pharmacokinetics of esomeprazole and short-term effect on serum gastrin levels and evaluate potential sex-related difference.

Materials and methods

Healthy volunteers received 40 mg of esomeprazole daily for five days. After the 1st and 5th dose blood samples for fasting gastrin and pharmacokinetic analysis were collected at scheduled time-points for eight hours. Esomeprazole was analysed by liquid chromatography and gastrin concentrations were measured using radioimmunoassay.

Results

A total of 30 volunteers were enrolled. Females had higher median baseline gastrin (pM) than males 12 (IQR 10–15) vs. 7 (IQR 4–11) (p = .03). In the study cohort, median gastrin levels rose from 10 (IQR 6–14) to 15 (IQR 13–20) (p = .0002). The serum levels for esomeprazole increased by an average of 299.8 ng/mL (p < .001) from day 1 to day 5. Comparison of the esomeprazole pharmacokinetic parameters between males and females revealed no significant sex-related differences. No significant correlation was found between the AUC and the gastrin level on day 5 (p = .15).

Conclusions

In healthy volunteers, serum gastrin increased significantly after a four-day PPI-therapy. There was also a significant increase in serum esomeprazole from day 1 to day 5. The increase in gastrin and esomeprazole concentration was not related to sex and no significant sex-related difference was found in terms of pharmacokinetic parameters. European Clinical Trial Database (2015-002230-41).

Keywords:

• Proton pump inhibitors
• gastrin
• pharmacokinetics
• sex-related difference
• pharmacology
• area under the serum concentration curve

Acknowledgements

We thank the Department of Clinical and Molecular Medicine at the Norwegian University of Science and Technology for the use of the home-made Gastin-Radioimmunoassay. We also thank the pharmaceutical company Actavis in Iceland for supplying the study medication and laboratory measurements of esomeprazole concentrations.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The original anonymous dataset is available on request from the corresponding author at [email protected].

Additional information

Funding

This work was supported by the University of Iceland Research Fund under Grant no. 140974-051 and funding from the Research Fund of the National University Hospital of Iceland was used in the preparation of this manuscript.