Oral esomeprazole in Japanese pediatric patients with gastric acid‐related disease: Safety, efficacy, and pharmacokinetics

Abstract

Background Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid‐related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid‐related disease, we conducted an 8 week, open‐label, parallel‐group, multicenter, phase I/III study of once‐daily oral esomeprazole use. Methods Japanese children, aged 1–14 years with gastric acid‐related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily. Results Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47–1.75 h, an arithmetic mean terminal elimination half‐life of 0.80–1.37 h, and a weight‐correlated apparent total body clearance of 0.216–0.343 L/h/kg. Area under the plasma concentration–time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty‐three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole. Conclusions Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children.

Integrated models of population pharmacokinetics and exposure response to optimize dosage regimen for anaprazole sodium in duodenal ulcer

“…This approach has received widespread attention from regulatory authorities ( FDA, 2022 ). According to previous studies ( Lew, 1999 ; Shimizu et al, 2019 ), PPIs are eliminated rapidly in vivo, to the extent that they cannot be detected in the blood shortly after administration. This poses a challenge for obtaining PK parameters and confirming the relationship between exposure and response.…”

Proton pump inhibitors: Oral treatment of pediatric disorders

“…In this issue of the Journal, Shimizu et al . report on the safety, tolerability, clinical efficacy, pharmacokinetics, and pharmacodynamics of esomeprazole, which is the only PPI approved in Japan for use in pediatric patients (≥1 year of age) with gastric acid‐related diseases, and conclude that no marked safety concerns are evident . Therefore, when selecting oral PPI for pediatric patients, it may be easier for physicians to choose esomeprazole.…”

“…Shimizu et al suggest that esomeprazole may be beneficial for use in H. pylori eradication therapy. 2 The Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition recently published their updated guidelines for the management of H. pylori infection in childhood. 3 Pediatric PPI doses (lansoprazole, omeprazole, rabeprazole, and esomeprazole) used for eradication of H. pylori are listed in these guidelines.…”

“…Shimizu et al . suggest that esomeprazole may be beneficial for use in H. pylori eradication therapy . The Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition recently published their updated guidelines for the management of H. pylori infection in childhood .…”