Ahmed M. Elmeniar, Mohamed A. Osman, Sanaa A. El-Gizawy, Dimple Modi, Nitin B. Charbe, Ayman F. El-Kattan, Mohamed El-Tanani, Yusuf A. Haggag, Murtaza M. Tambuwala
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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.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdd.2384","citationCount":"0","resultStr":"{\"title\":\"In situ evaluation of the impact of metformin or verapamil coadministration with vildagliptin on its regional absorption from the rabbit’s intestine\",\"authors\":\"Ahmed M. Elmeniar, Mohamed A. Osman, Sanaa A. El-Gizawy, Dimple Modi, Nitin B. Charbe, Ayman F. El-Kattan, Mohamed El-Tanani, Yusuf A. Haggag, Murtaza M. 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In situ evaluation of the impact of metformin or verapamil coadministration with vildagliptin on its regional absorption from the rabbit’s intestine
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.
期刊介绍:
Biopharmaceutics & Drug Dispositionpublishes original review articles, short communications, and reports in biopharmaceutics, drug disposition, pharmacokinetics and pharmacodynamics, especially those that have a direct relation to the drug discovery/development and the therapeutic use of drugs. These includes:
- animal and human pharmacological studies that focus on therapeutic response. pharmacodynamics, and toxicity related to plasma and tissue concentrations of drugs and their metabolites,
- in vitro and in vivo drug absorption, distribution, metabolism, transport, and excretion studies that facilitate investigations related to the use of drugs in man
- studies on membrane transport and enzymes, including their regulation and the impact of pharmacogenomics on drug absorption and disposition,
- simulation and modeling in drug discovery and development
- theoretical treatises
- includes themed issues and reviews
and exclude manuscripts on
- bioavailability studies reporting only on simple PK parameters such as Cmax, tmax and t1/2 without mechanistic interpretation
- analytical methods