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Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir

Proton-pump inhibitors (PPIs), frequently prescribed to lower gastric acid secretion, often exert an effect on the absorption of co-medicated drug products. A previous study showed decreased plasma levels of the lipophilic drug ritonavir after co-administration with the PPI Nexium (40 mg esomeprazol...

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Autores principales: de Waal, Tom, Rubbens, Jari, Grimm, Michael, Vandecaveye, Vincent, Tack, Jan, Weitschies, Werner, Brouwers, Joachim, Augustijns, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408179/
https://www.ncbi.nlm.nih.gov/pubmed/32708859
http://dx.doi.org/10.3390/pharmaceutics12070670
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author de Waal, Tom
Rubbens, Jari
Grimm, Michael
Vandecaveye, Vincent
Tack, Jan
Weitschies, Werner
Brouwers, Joachim
Augustijns, Patrick
author_facet de Waal, Tom
Rubbens, Jari
Grimm, Michael
Vandecaveye, Vincent
Tack, Jan
Weitschies, Werner
Brouwers, Joachim
Augustijns, Patrick
author_sort de Waal, Tom
collection PubMed
description Proton-pump inhibitors (PPIs), frequently prescribed to lower gastric acid secretion, often exert an effect on the absorption of co-medicated drug products. A previous study showed decreased plasma levels of the lipophilic drug ritonavir after co-administration with the PPI Nexium (40 mg esomeprazole), even though duodenal concentrations were not affected. The present study explored if a PPI-induced decrease in gastrointestinal (GI) fluid volume might contribute to the reduced absorption of ritonavir. In an exploratory cross-over study, five volunteers were given a Norvir tablet (100 mg ritonavir) orally, once without PPI pre-treatment and once after a three-day pre-treatment with the PPI esomeprazole. Blood samples were collected for eight hours to assess ritonavir absorption and magnetic resonance imaging (MRI) was used to determine the gastric and duodenal fluid volumes during the first three hours after administration of the tablet. The results confirmed that PPI intake reduced ritonavir plasma concentrations by 40%. The gastric residual volume and gastric fluid volume decreased by 41% and 44% respectively, while the duodenal fluid volume was reduced by 33%. These data suggest that the PPI esomeprazole lowers the available fluid volume for dissolution, which may limit the amount of ritonavir that can be absorbed. Although additional factors may play a role, the effect of PPI intake on the GI fluid volume should be considered when simulating the absorption of poorly soluble drugs like ritonavir in real-life conditions.
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spelling pubmed-74081792020-08-25 Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir de Waal, Tom Rubbens, Jari Grimm, Michael Vandecaveye, Vincent Tack, Jan Weitschies, Werner Brouwers, Joachim Augustijns, Patrick Pharmaceutics Article Proton-pump inhibitors (PPIs), frequently prescribed to lower gastric acid secretion, often exert an effect on the absorption of co-medicated drug products. A previous study showed decreased plasma levels of the lipophilic drug ritonavir after co-administration with the PPI Nexium (40 mg esomeprazole), even though duodenal concentrations were not affected. The present study explored if a PPI-induced decrease in gastrointestinal (GI) fluid volume might contribute to the reduced absorption of ritonavir. In an exploratory cross-over study, five volunteers were given a Norvir tablet (100 mg ritonavir) orally, once without PPI pre-treatment and once after a three-day pre-treatment with the PPI esomeprazole. Blood samples were collected for eight hours to assess ritonavir absorption and magnetic resonance imaging (MRI) was used to determine the gastric and duodenal fluid volumes during the first three hours after administration of the tablet. The results confirmed that PPI intake reduced ritonavir plasma concentrations by 40%. The gastric residual volume and gastric fluid volume decreased by 41% and 44% respectively, while the duodenal fluid volume was reduced by 33%. These data suggest that the PPI esomeprazole lowers the available fluid volume for dissolution, which may limit the amount of ritonavir that can be absorbed. Although additional factors may play a role, the effect of PPI intake on the GI fluid volume should be considered when simulating the absorption of poorly soluble drugs like ritonavir in real-life conditions. MDPI 2020-07-17 /pmc/articles/PMC7408179/ /pubmed/32708859 http://dx.doi.org/10.3390/pharmaceutics12070670 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
de Waal, Tom
Rubbens, Jari
Grimm, Michael
Vandecaveye, Vincent
Tack, Jan
Weitschies, Werner
Brouwers, Joachim
Augustijns, Patrick
Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir
title Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir
title_full Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir
title_fullStr Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir
title_full_unstemmed Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir
title_short Exploring the Effect of Esomeprazole on Gastric and Duodenal Fluid Volumes and Absorption of Ritonavir
title_sort exploring the effect of esomeprazole on gastric and duodenal fluid volumes and absorption of ritonavir
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408179/
https://www.ncbi.nlm.nih.gov/pubmed/32708859
http://dx.doi.org/10.3390/pharmaceutics12070670
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