Cargando…

Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects

BACKGROUND: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Hyun Chul, Yang, Eunsol, Ban, Mu Seong, Kim, Yu Kyong, Hong, Sung Hee, Jung, Jina, Jang, In-Jin, Lee, SeungHwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106809/
https://www.ncbi.nlm.nih.gov/pubmed/37077412
http://dx.doi.org/10.2147/DDDT.S392533
_version_ 1785026488533254144
author Kim, Hyun Chul
Yang, Eunsol
Ban, Mu Seong
Kim, Yu Kyong
Hong, Sung Hee
Jung, Jina
Jang, In-Jin
Lee, SeungHwan
author_facet Kim, Hyun Chul
Yang, Eunsol
Ban, Mu Seong
Kim, Yu Kyong
Hong, Sung Hee
Jung, Jina
Jang, In-Jin
Lee, SeungHwan
author_sort Kim, Hyun Chul
collection PubMed
description BACKGROUND: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression. PURPOSE: This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects. METHODS: Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose. RESULTS: In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration–time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration–time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00–06:00) showed a better tendency in the DR formulation. CONCLUSION: The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.
format Online
Article
Text
id pubmed-10106809
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-101068092023-04-18 Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects Kim, Hyun Chul Yang, Eunsol Ban, Mu Seong Kim, Yu Kyong Hong, Sung Hee Jung, Jina Jang, In-Jin Lee, SeungHwan Drug Des Devel Ther Original Research BACKGROUND: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression. PURPOSE: This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects. METHODS: Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose. RESULTS: In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration–time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration–time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00–06:00) showed a better tendency in the DR formulation. CONCLUSION: The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms. Dove 2023-04-12 /pmc/articles/PMC10106809/ /pubmed/37077412 http://dx.doi.org/10.2147/DDDT.S392533 Text en © 2023 Kim et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Kim, Hyun Chul
Yang, Eunsol
Ban, Mu Seong
Kim, Yu Kyong
Hong, Sung Hee
Jung, Jina
Jang, In-Jin
Lee, SeungHwan
Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects
title Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects
title_full Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects
title_fullStr Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects
title_full_unstemmed Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects
title_short Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects
title_sort pharmacokinetics and pharmacodynamics of esomezol dr, a new dual delayed-release formulation of esomeprazole 20 mg or 40 mg, in healthy subjects
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106809/
https://www.ncbi.nlm.nih.gov/pubmed/37077412
http://dx.doi.org/10.2147/DDDT.S392533
work_keys_str_mv AT kimhyunchul pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects
AT yangeunsol pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects
AT banmuseong pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects
AT kimyukyong pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects
AT hongsunghee pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects
AT jungjina pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects
AT janginjin pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects
AT leeseunghwan pharmacokineticsandpharmacodynamicsofesomezoldranewdualdelayedreleaseformulationofesomeprazole20mgor40mginhealthysubjects