Influence of osmolality on gastrointestinal fluid volume and drug absorption: potential impact on oral salt supplementation.
Drug absorption
Gastrointestinal tract
Membrane permeability
Osmolality
Pharmacokinetics
Journal
Journal of pharmaceutical health care and sciences
ISSN: 2055-0294
Titre abrégé: J Pharm Health Care Sci
Pays: England
ID NLM: 101672177
Informations de publication
Date de publication:
01 Sep 2021
01 Sep 2021
Historique:
received:
02
04
2021
accepted:
10
06
2021
entrez:
1
9
2021
pubmed:
2
9
2021
medline:
2
9
2021
Statut:
epublish
Résumé
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the most frequent cause of hyponatremia in patients with cerebrovascular disease, and is often treated with oral salt tablets. However, we have shown that osmolality-dependent variations in gastrointestinal (GI) fluid volume can alter the concentration of a poorly permeable drug in the GI tract, potentially affecting its absorption. Here, we examined the effect of ingestion of hyperosmotic solution (10% NaCl) on drug concentration and absorption in the GI tract. The effects of osmolality on luminal fluid volume and drug absorption in rat intestine (jejunum, ileum and colon) were examined by means of an in situ closed loop method using fluorescein isothiocyanate-dextran 4000 (FD-4) and atenolol. In vivo absorption in rats was determined by measuring the plasma concentration after oral administration of the test compounds dissolved in purified water or hyperosmotic solution (10% NaCl). Administration of hyperosmotic solution directly into the GI tract significantly increased the GI fluid volume, owing to secretion of water into the lumen. After administration in hyperosmotic solution, the luminal concentration of non-permeable FD-4 was significantly lower than the initial dosing concentration, whereas after administration in purified water, the luminal concentration exceeded the initial concentration. The fraction absorbed of atenolol was markedly lower after administration in hyperosmotic solution than after administration in purified water. An in vivo pharmacokinetic study in rats was consistent with these findings. Administration of hyperosmotic NaCl solution increased GI fluid volume and reduced the plasma level of orally administered atenolol. This may imply that oral salt tablets used to treat hyponatremia in SIADH patients could decrease the intestinal absorption of concomitantly administered drugs, resulting in lower plasma exposure.
Sections du résumé
BACKGROUND
BACKGROUND
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the most frequent cause of hyponatremia in patients with cerebrovascular disease, and is often treated with oral salt tablets. However, we have shown that osmolality-dependent variations in gastrointestinal (GI) fluid volume can alter the concentration of a poorly permeable drug in the GI tract, potentially affecting its absorption. Here, we examined the effect of ingestion of hyperosmotic solution (10% NaCl) on drug concentration and absorption in the GI tract.
METHODS
METHODS
The effects of osmolality on luminal fluid volume and drug absorption in rat intestine (jejunum, ileum and colon) were examined by means of an in situ closed loop method using fluorescein isothiocyanate-dextran 4000 (FD-4) and atenolol. In vivo absorption in rats was determined by measuring the plasma concentration after oral administration of the test compounds dissolved in purified water or hyperosmotic solution (10% NaCl).
RESULTS
RESULTS
Administration of hyperosmotic solution directly into the GI tract significantly increased the GI fluid volume, owing to secretion of water into the lumen. After administration in hyperosmotic solution, the luminal concentration of non-permeable FD-4 was significantly lower than the initial dosing concentration, whereas after administration in purified water, the luminal concentration exceeded the initial concentration. The fraction absorbed of atenolol was markedly lower after administration in hyperosmotic solution than after administration in purified water. An in vivo pharmacokinetic study in rats was consistent with these findings.
CONCLUSIONS
CONCLUSIONS
Administration of hyperosmotic NaCl solution increased GI fluid volume and reduced the plasma level of orally administered atenolol. This may imply that oral salt tablets used to treat hyponatremia in SIADH patients could decrease the intestinal absorption of concomitantly administered drugs, resulting in lower plasma exposure.
Identifiants
pubmed: 34465382
doi: 10.1186/s40780-021-00212-z
pii: 10.1186/s40780-021-00212-z
pmc: PMC8408929
doi:
Types de publication
Journal Article
Langues
eng
Pagination
29Subventions
Organisme : Japan Society for the Promotion of Science
ID : 20K07165
Informations de copyright
© 2021. The Author(s).
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