TY - JOUR
T1 - Rectal Omeprazole in Infants With Gastroesophageal Reflux Disease: A Randomized Pilot Trial
AU - Bestebreurtje, Petra
AU - de Koning, Barbara A. E.
AU - Roeleveld, Nel
AU - Knibbe, Catherijne A. J.
AU - Tibboel, Dick
AU - van Groen, Bianca
AU - van de Ven, Cees P.
AU - Plötz, Frans B.
AU - de Wildt, Saskia N.
N1 - Funding Information: This work was supported by Fonds Nuts Ohra Grant number 1103-049. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Background and Objective: Omeprazole is a proton pump inhibitor that is used in acid suppression therapy in infants. Infants cannot swallow the oral tablets or capsules. Since, infants require a non-standard dose of omeprazole, the granules or tablets are often crushed or suspended in water or sodium bicarbonate, which may destroy the enteric coating. In this study we explore the efficacy and pharmacokinetics of rectally administered omeprazole in infants with gastroesophageal reflux disease (GERD) due to esophageal atresia (EA) or congenital diaphragmatic hernia (CDH) and compare these with orally administered omeprazole. Methods: Infants (6–12 weeks postnatal and bodyweight > 3 kg) with EA or CDH and GERD were randomized to receive a single dose of 1 mg/kg omeprazole rectally or orally. The primary outcome was the percentage of infants for whom omeprazole was effective according to predefined criteria for 24-h intraesophageal pH. Secondary outcomes were the percentages of time that gastric pH was < 3 or < 4, as well as the pharmacokinetic parameters. Results: Seventeen infants, 4 with EA and 13 with CDH, were included. The proportion of infants for whom omeprazole was effective was 56% (5 of 9 infants) after rectal administration and 50% (4 of 8 infants) after oral administration. The total reflux time in minutes and percentages and the number of reflux episodes of pH < 4 decreased statistically significantly after both rectal and oral omeprazole administration. Rectal and oral administration of omeprazole resulted in similar serum exposure. Conclusions: A single rectal omeprazole dose (1 mg/kg) results in consistent increases in intraesophageal and gastric pH in infants with EA- or CDH-related GERD, similar to an oral dose. Considering the challenges with existing oral formulations, rectal omeprazole presents as an innovative, promising alternative for infants with pathological GERD. Clinical Trial Register: ClinicalTrials.gov Identifier: NCT00226044.
AB - Background and Objective: Omeprazole is a proton pump inhibitor that is used in acid suppression therapy in infants. Infants cannot swallow the oral tablets or capsules. Since, infants require a non-standard dose of omeprazole, the granules or tablets are often crushed or suspended in water or sodium bicarbonate, which may destroy the enteric coating. In this study we explore the efficacy and pharmacokinetics of rectally administered omeprazole in infants with gastroesophageal reflux disease (GERD) due to esophageal atresia (EA) or congenital diaphragmatic hernia (CDH) and compare these with orally administered omeprazole. Methods: Infants (6–12 weeks postnatal and bodyweight > 3 kg) with EA or CDH and GERD were randomized to receive a single dose of 1 mg/kg omeprazole rectally or orally. The primary outcome was the percentage of infants for whom omeprazole was effective according to predefined criteria for 24-h intraesophageal pH. Secondary outcomes were the percentages of time that gastric pH was < 3 or < 4, as well as the pharmacokinetic parameters. Results: Seventeen infants, 4 with EA and 13 with CDH, were included. The proportion of infants for whom omeprazole was effective was 56% (5 of 9 infants) after rectal administration and 50% (4 of 8 infants) after oral administration. The total reflux time in minutes and percentages and the number of reflux episodes of pH < 4 decreased statistically significantly after both rectal and oral omeprazole administration. Rectal and oral administration of omeprazole resulted in similar serum exposure. Conclusions: A single rectal omeprazole dose (1 mg/kg) results in consistent increases in intraesophageal and gastric pH in infants with EA- or CDH-related GERD, similar to an oral dose. Considering the challenges with existing oral formulations, rectal omeprazole presents as an innovative, promising alternative for infants with pathological GERD. Clinical Trial Register: ClinicalTrials.gov Identifier: NCT00226044.
UR - http://www.scopus.com/inward/record.url?scp=85087294259&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s13318-020-00630-8
DO - https://doi.org/10.1007/s13318-020-00630-8
M3 - Article
C2 - 32594305
SN - 0378-7966
VL - 45
SP - 635
EP - 643
JO - European Journal of Drug Metabolism and Pharmacokinetics
JF - European Journal of Drug Metabolism and Pharmacokinetics
IS - 5
ER -