Pharmacokinetics and Acid‐suppressive Effects of Esomeprazole in Infants 1–24 Months Old With Symptoms of Gastroesophageal Reflux Disease

Omari, Taher; Davidson, Geoffrey P.; Bondarov, Patrik; Nauclér, Emma; Nilsson, Carin; Lundborg, Per

doi:10.1097/mpg.0b013e31812e012f

Cited by 51 publications

(26 citation statements)

References 30 publications

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“…In general, the exposure increased more than proportionately with an increase in dose, from 10 mg to 20 mg. The inter‐individual variability, as well as the age, weight and dose dependency are all consistent with previous findings in Japanese adults, and in Caucasian children . The more pronounced variability in children may be partly explained by the lower number of plasma samples in children, potential loss of substance/dose due to spitting/vomiting in some smaller children, and, further, the age‐dependent maturation of the CYP liver enzymes …”

Section: Discussionsupporting

confidence: 88%

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

Shimizu

Nakayama

Ishii

et al. 2019

Pediatrics International

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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.

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Section: Discussionsupporting

confidence: 88%

“…Although the number of patients who consented to intragastric pH monitoring was small, a longer duration of gastric pH >4 with esomeprazole treatment was indicated, as has been seen in previous studies in Japanese adults (Dr Per Lundbord, unpubl. data, 2004) and Caucasian children …”

Section: Discussionmentioning

confidence: 99%

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

Shimizu

Nakayama

Ishii

et al. 2019

Pediatrics International

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“…Notable works that may translate to neonatal population include: 1) development of automated impedance manometry for pressure flow analysis 63,68–70 , 2) effect of GERD therapies in infants and children 71–77 , and the 3) effect of stimulus characteristics on esophageal function 78,79 .…”

Section: ) Pathophysiology Of Aerodigestive Systemsmentioning

confidence: 99%

Advances with Neonatal Aerodigestive Science in the Pursuit of Safe Swallowing in Infants: Invited Review

Jadcherla

2017

Dysphagia

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Feeding, swallowing and airway protection are three distinct entities. Feeding involves a process of sequential, neurosensory and neuromotor interactions of reflexes and behaviors facilitating ingestion. Swallowing involves anterograde bolus movement during oral-, pharyngeal- and esophageal phases of peristalsis into stomach. During these events, coordination with airway protection is vital for homeostasis in clearing any material away from airway vicinity. Neurological-airway-digestive inter-relationships are critical to the continuum of successful feeding patterns during infancy, either in health or disease. Neonatal feeding difficulties encompass a heterogeneous group of neurological, pulmonary and aerodigestive disorders that present with multiple signs posing as clinical conundrums. Significant research breakthroughs permitted understanding of vagal neural pathways and functional aerodigestive connectivity involved in regulating swallowing and aerodigestive functions either directly or indirectly by influencing the supra-nuclear regulatory centers and peripheral effector organs. These neurosensory and neuromotor pathways are influenced by pathologies during perinatal events, prematurity, inflammatory states and coexisting medical and surgical conditions. Approaches to clarify pathophysiologic mapping of aerodigestive interactions, as well as translating these discoveries into the development of personalized and simplified feeding strategies to advance child health are discussed in this review article.

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“…On the contrary, a recent study by Omari et al [92], on the effectiveness of esomeprazole in preterm infants, demonstrated a significant decrease in the number of GERD-related symptoms, a remarkable reduction of the overall esophageal acid exposure and, as previously found [93], a lowered number of acid bolus reflux episodes whereas, as expected, nonacid GER features were not influenced. However, these results were not controlled for placebo effects; therefore, they should be confirmed in further placebo-controlled trials.…”

Section: Pharmacological Therapymentioning

confidence: 46%

Pharmacological Therapy of Gastroesophageal Reflux in Preterm Infants

Corvaglia

Monari

Martini

et al. 2013

Gastroenterology Research and Practice

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Although gastroesophageal reflux (GER) is a very common phenomenon among preterm infants, its therapeutic management is still an issue of debate among neonatologists. A step-wise approach should be advisable, firstly promoting nonpharmacological interventions and limiting drugs to selected infants unresponsive to the conservative measures or who are suffering from severe GER with clinical complications. Despite of this, a concerning pharmacological overtreatment has been increasingly reported. Most of the antireflux drugs, however, have not been specifically assessed in preterm infants; moreover, serious adverse effects have been noticed in association to their administration. This review mainly aims to draw the state of the art regarding the pharmacological management of GER in preterm infants, analyzing the best piecies of evidence currently available on the most prescribed anti-reflux drugs. Although further trials are required, sodium alginate-based formulations might be considered promising; however, data regarding their safety are still limited. Few piecies of evidence on the efficacy of histamine-2 receptor blockers and proton pump inhibitors in preterm infants with GER are currently available. Nevertheless, a significantly increased risk of necrotizing enterocolitis and infections has been largely reported in association with their use, thereby leading to an unfavorable risk-benefit ratio. The efficacy of metoclopramide in GER's improvement still needs to be clarified. Other prokinetic agents, such as domperidone and erythromycin, have been reported to be ineffective, whereas cisapride has been withdrawn due to its remarkable cardiac adverse effects.

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Pharmacokinetics and Acid‐suppressive Effects of Esomeprazole in Infants 1–24 Months Old With Symptoms of Gastroesophageal Reflux Disease

Abstract: Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well tolerated and provided dose-related acid suppression, dose-related exposure to esomeprazole, and decreased esophageal acid exposure in infants 1-24 months old with GERD.

Cited by 51 publications

References 30 publications

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

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

Advances with Neonatal Aerodigestive Science in the Pursuit of Safe Swallowing in Infants: Invited Review

Pharmacological Therapy of Gastroesophageal Reflux in Preterm Infants

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