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

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).

Automated summary

In healthy volunteers, serum gastrin levels significantly increased after four-day PPI therapy, along with a significant rise in serum esomeprazole concentration. There were no significant sex-related differences in terms of pharmacokinetic parameters, and no significant correlation was found between the AUC and gastrin levels on day 5.