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

Tom De Waal,Joachim Brouwers,Patrick Augustijns,Michael Grimm,Vincent Vandecaveye,Jari Rubbens,Jan Tack,Werner Weitschies

doi:10.3390/pharmaceutics12070670

Tom De Waal, Joachim Brouwers + Show 6 more

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https://doi.org/10.3390/pharmaceutics12070670

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Journal: Pharmaceutics	Publication Date: Jul 17, 2020
Citations: 15	License type: CC BY 4.0

Affiliation: KU Leuven, University of Greifswald

Abstract

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.

Highlights

Since their introduction three decades ago, proton-pump inhibitors (PPI) have taken over as the leading drug class in the treatment and prevention of various gastric acid related diseases (e.g., gastroesophageal reflux disease (GERD), peptic ulcer bleeding and non-steroidal anti-inflammatory drug (NSAID) induced ulcers) [1]
To confirm the effect of pre-treatment with the PPI esomeprazole on the absorption and systemic disposition of ritonavir, its plasma concentrations were determined after intake of a not use the ritonavir amorphous solid dispersion (Norvir) tablet
The effect of the PPI esomeprazole on the absorption of ritonavir has previously been investigated by Van Den Abeele et al, who first discovered that a decreased systemic exposure to ritonavir upon PPI pre-treatment could not be explained by a reduced driving force for absorption as the duodenal concentrations of ritonavir were unaffected [13]

Summary

Introduction

Since their introduction three decades ago, proton-pump inhibitors (PPI) have taken over as the leading drug class in the treatment and prevention of various gastric acid related diseases (e.g., gastroesophageal reflux disease (GERD), peptic ulcer bleeding and non-steroidal anti-inflammatory drug (NSAID) induced ulcers) [1]. Their mechanism of action is related to the covalent binding of the PPI to the H+/K+ ATPase in the acid secreting parietal cells. As PPIs are so frequently (over)prescribed, concern has recently been risen regarding the adverse effects of prolonged PPI treatment. Malabsorption of calcium, iron, magnesium and vitamin B12 are reported as their absorption depends on the acidic gastric fluid [3]

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