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

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.

A phantom to simulate organ motion and its effect on dose distribution in carbon ion therapy for pancreatic cancer

“…The filling and emptying of the duodenum were done with water and therefore its movement was realized by connecting the tube to a 50 ml syringe. For emptying the duodenum, 25 ml of the water was suctioned out of it, representing a reduction of 8.6% of its total volume, in agreement with other studies (Mudie et al 2014, Waal et al 2020. In both states, full (control) and empty, measurements with a 3 T MRI scanner (Biograph mMR, Siemens Healthineers, Germany) were conducted using a T1 vibe Dixon sequence with a resolution of (1 × 1 × 1) mm 3 to measure the duodenum shape as its distance to the pancreas.…”

Gastrointestinal Fluid Volumes in Pediatrics: A Retrospective MRI Study

“…Images were analyzed to calculate fluid volumes in the GI tract using Horos TM (Version 3.3.6, Horosproject.org sponsored by Nimble Co LLC d/b/a Purview, Annapolis, MD USA), a free and open-source code software (FOSS) medical image viewer. Integration of free fluid was performed in accordance with the protocol published by de Waal et al [22]. In brief, free fluid has a high signal intensity on T2-weighted images.…”

“…Manual corrections were performed to exclude the fluid outside the GI tract (e.g., gallbladder, urinary tract, spinal canal, interstitial fluid). The integration did not include the heterogeneous hyper-to iso-intense fluid that is present in the distal small and large intestine as digested food [19,22].…”

“…Additionally, it is important to understand the distribution of fluid over the GI tract, since sufficient fluid should be available at the absorption site of the drug. In this respect, magnetic resonance imaging (MRI) has already proven its value to localize and quantify fluid volumes in the stomach and intestine of adults [17,[19][20][21][22], providing valuable input data for biorelevant in vitro dissolution tests and PBPK modeling [17,23].…”

The effect of esomeprazole on the upper GI tract release and systemic absorption of mesalazine from colon targeted formulations

“…In particular, the absorption of various poorly soluble weakly basic drugs, depending on adequate dissolution in the acidic stomach, significantly drops upon PPI intake. In addition, PPI treatment may reduce the available gastric and duodenal fluid volumes, again affecting dissolution and absorption of poorly soluble drugs (de Waal et al, 2020).…”