Study on enteral nutrient components causing decreased gastric phenytoin absorption.

Autor: Urashima Y; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Ueno T; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Takeda C; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Kusaba H; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Tanaka R; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Noda K; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Kawakami K; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Murakami T; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Kawaguchi A; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Suemitsu Y; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Urashima K; Department of Pharmacy, Japan Community Health Care Organization Hoshigaoka Medical Center, Osaka, Japan., Suzuki K; Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan., Kurachi K; Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan., Nishihara M; Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan., Neo M; Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan., Myotoku M; Laboratory of Practical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Kobori T; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan., Obata T; Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan.
Jazyk: angličtina
Zdroj: JPEN. Journal of parenteral and enteral nutrition [JPEN J Parenter Enteral Nutr] 2023 Sep; Vol. 47 (7), pp. 911-919. Date of Electronic Publication: 2023 Jul 17.
DOI: 10.1002/jpen.2542
Abstrakt: Background: Previously, we revealed that coadministration of particular enteral nutrients (ENs) decreases plasma concentrations and gastric absorption of phenytoin (PHT), an antiepileptic drug, in rats; however, the mechanism has not been clarified.
Methods: We measured the permeability rate of PHT using a Caco-2 cell monolayer as a human intestinal absorption model with casein, soy protein, simulated gastrointestinal digested casein protein (G-casein or P-casein) or simulated gastrointestinal digested soy protein (G-soy or P-soy), dextrin, sucrose, degraded guar gum, indigestible dextrin, calcium, and magnesium, which are abundant in the ENs, and measured the solution's properties.
Results: We demonstrated that casein (40 mg/ml), G-soy or P-soy (10 mg/ml), and dextrin (100 mg/ml) significantly decreased the permeability rate of PHT compared with the control. By contrast, G-casein or P-casein significantly increased the permeability rate of PHT. We also found that the PHT binding rate to casein 40 mg/ml was 90%. Furthermore, casein 40 mg/ml and dextrin 100 mg/ml have high viscosity. Moreover, G-casein and P-casein significantly decreased the transepithelial electrical resistance of Caco-2 cell monolayers compared with casein and the control.
Conclusion: Casein, digested soy protein, and dextrin decreased the gastric absorption of PHT. However, digested casein decreased PHT absorption by reducing the strength of tight junctions. The composition of ENs may affect the absorption of PHT differently, and these findings would aid in the selection of ENs for orally administered PHT.
(© 2023 American Society for Parenteral and Enteral Nutrition.)
Databáze: MEDLINE
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