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Information Journal Paper

Title

An Investigation into the Role of P-Glycoprotein in the Intestinal Absorption of Repaglinide: Assessed by Everted Gut Sac and Caco-2 Cell Line

Pages

  102-110

Abstract

 The present study aimed at exploring the potential of the P-glycoprotein (P-gp) transporters as a barrier to the Repaglinide (REG) epithelial Permeability. In-vitro intestinal absorption models, the Everted gut sac, and Caco-2 cell line, were used to study the possible role of P-gp in intestinal transport of REG. In the Everted gut sacs, apparent Permeability coefficients showed cargo concentration dependency transport over the concentration of 40 μ M, indicating involvement of a saturable mechanism in REG absorption (Papp were 1. 23 × 10-5 and 3. 29 × 10-5 at drug concentrations of 40 and 100 μ M, respectively). Adding verapamil (100 μ M), valspodar (5 μ M) and ketoconazole (10 μ M) significantly enhanced the Permeability of REG across mucosal to serosal in the rat jejunum (P < 0. 05) suggesting role of CYP 3A4 and/ or efflux transporters in oral bioavailability of REG. However, the results of Caco-2 cell experiments indicated low efflux ratios (less than 2) and insignificant involvement of P-gp efflux pumps in REG intestinal transport. Given that Caco-2 Cells do not express adequate level of CYP 3A4, the current study suggests that the presystemic metabolism by cytochrome P450 (and not ejection by P-gp) may play a significant role in limiting the oral absorption of REG in small intestine.

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    APA: Copy

    Yaghoobian, Morteza, HAERI, AZADEH, BOLOURCHIAN, NOUSHIN, SHAHHOSSEINI, SORAYA, & DADASHZADEH, SIMIN. (2019). An Investigation into the Role of P-Glycoprotein in the Intestinal Absorption of Repaglinide: Assessed by Everted Gut Sac and Caco-2 Cell Line. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 18(1), 102-110. SID. https://sid.ir/paper/289198/en

    Vancouver: Copy

    Yaghoobian Morteza, HAERI AZADEH, BOLOURCHIAN NOUSHIN, SHAHHOSSEINI SORAYA, DADASHZADEH SIMIN. An Investigation into the Role of P-Glycoprotein in the Intestinal Absorption of Repaglinide: Assessed by Everted Gut Sac and Caco-2 Cell Line. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2019;18(1):102-110. Available from: https://sid.ir/paper/289198/en

    IEEE: Copy

    Morteza Yaghoobian, AZADEH HAERI, NOUSHIN BOLOURCHIAN, SORAYA SHAHHOSSEINI, and SIMIN DADASHZADEH, “An Investigation into the Role of P-Glycoprotein in the Intestinal Absorption of Repaglinide: Assessed by Everted Gut Sac and Caco-2 Cell Line,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 18, no. 1, pp. 102–110, 2019, [Online]. Available: https://sid.ir/paper/289198/en

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