Effect of ingested fluid volume and solution osmolality on intestinal drug absorption: Impact on drug interaction with beverages

Funai, Yuta; Takemura, Motohide; Inoue, Katsuhisa; Shirasaka, Yoshiyuki

doi:10.1016/j.ejps.2022.106136

Cited by 8 publications

(4 citation statements)

References 48 publications

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“…We recently reported that changes in the GI fluid volume may indirectly influence the drug absorption profile by altering the drug concentration and absorption kinetics 1 – 5 . Furthermore, we and other research groups demonstrated that water secretion and drug resultant dilution of drug concentration in the GI tract may contribute to beverage-drug interactions that result in decreased drug absorption 1 , 6 , 7 . Thus, it has been noted that GI fluid dynamics concepts to date are not sufficient for the development of oral drug delivery and prediction of oral drug absorption 8 .…”

Section: Introductionmentioning

confidence: 74%

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Quantitative analysis of gastrointestinal fluid absorption and secretion to estimate luminal fluid dynamics in rats

Funai,

Ichijo,

Suzuki

et al. 2023

Sci Rep

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The drug absorption profile is dependent on the luminal drug concentration, which in turn is influenced by the gastrointestinal (GI) fluid dynamics. In the present study, therefore, we aimed to examine the luminal fluid dynamics by kinetically analyzing fluid absorption and secretion along the GI tract in rats using the in situ closed-loop technique with non-absorbable fluorescein isothiocyanate-dextran 4000 (FD-4) and tritium water labeling ([3H]water) under different osmotic conditions. We found that the luminal fluid volume in the jejunum and ileum, but not the colon, gradually decreased and reached a steady state. In contrast, [3H]water almost completely disappeared in all intestinal regions. Kinetic analysis revealed the following rank order for the rate constant of fluid secretion: jejunum > ileum > colon, whereas a negligible regional difference was observed in the rate constant of fluid absorption. Fluid secretion under an isosmotic condition (300 mOsm/kg) was higher than that at 0 mOsm/kg in all intestinal regions, though no significant changes in fluid absorption were observed. Thus, the fluid secretion process appears to be the major determinant of the regional differences in GI fluid dynamics. Our findings indicate that the luminal fluid volume is altered as a result of water ingestion, absorption, and secretion, and finally reaches an apparent steady state, which is regulated mainly by the process of fluid secretion.

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Section: Introductionmentioning

confidence: 74%

“…The fluid volume and drug concentration in the rat GI tract were determined using the in situ closed-loop methods described by Funai et al 1 , 7 . Before the experiments, rats were fasted for at least 12 h with free access to water.…”

Section: Methodsmentioning

confidence: 99%

Quantitative analysis of gastrointestinal fluid absorption and secretion to estimate luminal fluid dynamics in rats

Funai,

Ichijo,

Suzuki

et al. 2023

Sci Rep

Self Cite

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“…10,13) We recently reported that the concomitant ingestion of AJ reduces GI absorption of atenolol due to a decrease in the luminal drug concentration resulting from osmotic fluid secretion into the GI lumen. 13,15) Not only AJ but also OJ has been reported to interact with atenolol absorption, although there are no reports so far examining whether or not GFJ has a clinically relevant effect. 10,11) Since all FJs have high osmolality as described in Results, it seems likely that they decrease the GI absorption of atenolol via the same mechanism as AJ (i.e., osmolality-dependent fluid secretion).…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, ingestion of AJ leads to fluid secretion into the GI lumen due to the high osmolality of AJ, resulting in a reduction of GI absorption of atenolol owing to its reduced concentration in the GI fluid. 13,15) Therefore, variations in GI fluid secretion depending on the osmolality of ingested FJ might explain the reported phenomenon that the decrease in the plasma concentration of atenolol is greater with coadministration of AJ than with OJ. 10,11) In the present study, we investigated whether osmolalitydependent fluid secretion into the GI lumen can explain the differences in the magnitude of FJ-drug interactions depending on the type of FJ.…”

Section: Introductionmentioning

confidence: 99%

Magnitude of Fruit Juice–Drug Interactions Due to Osmolality-Dependent Fluid Secretion: Differences among Apple, Orange, and Grapefruit Juices

Takemura,

Inoue,

Tamai

et al. 2024

Biological & Pharmaceutical Bulletin

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We recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug interactions. Here, we investigated whether osmolality-dependent fluid secretion can explain the difference in the magnitudes of fruit juice-drug interactions depending on the type of fruit juice (grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ)). The osmolality of GFJ, OJ, and AJ used in this study was found to be 552, 686, and 749 mOsm/kg, respectively. Measurements of intestinal fluid movement following beverage administration by the in situ closedloop technique revealed the following rank order for fluid volume in rat ileum: AJ > OJ > GFJ > purified water, suggesting that water movement is dependent on the osmolality of these beverages. Such changes in GI fluid volume are expected to alter the luminal drug concentration, potentially contributing to the magnitude of beverage-drug interactions. Indeed, in vivo pharmacokinetic study in rats revealed that the plasma concentration of atenolol, a low-permeability drug, was the highest after oral administration in purified water, followed by GFJ and OJ, and was the lowest after administration in AJ. In contrast, antipyrine, a highpermeability drug, showed no significant difference in plasma concentration after administration in purified water and fruit juices, suggesting that the absorption of high-permeability drugs is less affected by solution osmolality. Our findings indicate that differences in the magnitude of beverage-drug interactions can be at least partly explained by differences in the osmolality of the beverages ingested.

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Food effects on gastrointestinal physiology and drug absorption

Kambayashi

Shirasaka

2023

Drug Metabolism and Pharmacokinetics

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Effect of ingested fluid volume and solution osmolality on intestinal drug absorption: Impact on drug interaction with beverages

Cited by 8 publications

References 48 publications

Quantitative analysis of gastrointestinal fluid absorption and secretion to estimate luminal fluid dynamics in rats

Quantitative analysis of gastrointestinal fluid absorption and secretion to estimate luminal fluid dynamics in rats

Magnitude of Fruit Juice–Drug Interactions Due to Osmolality-Dependent Fluid Secretion: Differences among Apple, Orange, and Grapefruit Juices

Food effects on gastrointestinal physiology and drug absorption

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