In situ evaluation of the impact of metformin or verapamil coadministration with vildagliptin on its regional absorption from the rabbit's intestine.

Autor: Elmeniar AM; Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science & Technology, Belkas, Egypt., Osman MA; Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt., El-Gizawy SA; Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt., Modi D; Department of Pharmaceutical Sciences, Saint Joseph's University, Philadelphia, Pennsylvania, USA., Charbe NB; Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida, USA., El-Kattan AF; IFM Therapeutics, Boston, Massachusetts, USA., El-Tanani M; College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates., Haggag YA; Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt., Tambuwala MM; College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.; Lincoln Medical School - Universities of Nottingham and Lincoln, University of Lincoln, Lincolnshire, UK.
Jazyk: angličtina
Zdroj: Biopharmaceutics & drug disposition [Biopharm Drug Dispos] 2024 Apr; Vol. 45 (2), pp. 71-82. Date of Electronic Publication: 2024 Feb 24.
DOI: 10.1002/bdd.2384
Abstrakt: This research aims to identify regional differences in vildagliptin absorption across the intestinal membrane. Furthermore, it was to investigate the effect of verapamil or metformin on vildagliptin absorptive clearance. The study utilized an in situ rabbit intestinal perfusion technique to determine vildagliptin oral absorption from duodenum, jejunum, ileum, and ascending colon. This was conducted both with and without perfusion of metformin or verapamil. The findings revealed that the vildagliptin absorptive clearance per unit length varied by site and was in the order as follows: ileum < jejunum < duodenum < ascending colon, implying that P-gp is significant in the reduction of vildagliptin absorption. Also, the arrangement cannot reverse intestinal P-gp, but the observations suggest that P-gp is significant in reducing vildagliptin absorption. Verapamil co-perfusion significantly increased the vildagliptin absorptive clearance by 2.4 and 3.2 fold through the jejunum and ileum, respectively. Metformin co-administration showed a non-significant decrease in vildagliptin absorptive clearance through all tested segments. Vildagliptin absorption was site-dependent and may be related to the intestinal P-glycoprotein content. This may aid in understanding the important elements that influence vildagliptin absorption, besides drug-drug interactions that can occur in type 2 diabetic patients taking vildagliptin in conjunction with other drugs that can modify the P-glycoprotein level.
(© 2024 The Authors. Biopharmaceutics & Drug Disposition published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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