Investigation of Intestinal Permeability of Anti-Cancer Agent, Paclitaxel

Abstract

Background: The intestinal permeability of paclitaxel (PTX) in male wistar rats using Single Pass Intestinal Perfusion (SPIP) method was assessed. PTX has limitations in penetrating to and being absorbed from the intestine due to its low permeability and solubility. Aim: We hypothesized that PTX is a substrate for permeability glycoprotein (P-gp), therefore verapamil (VPL) was used in PTX’s solutions to inhibit P-gp and enhance permeability of PTX into the intestine. Materials and methods: PTX solution and PTX in combination with VPL were perfused separately by a syringe pump into the cannulated intestine with SPIP method and samples were taken and were analyzed by High Performance Lipid Chromatography (HPLC) method and permeability coefficients (P eff) were calculated. For correcting water efflux through the rat intestine, Phenol Red (PR) solution were utilized. Results: The effect of increasing the concentration of PTX and PTX + VPL on its intestinal permeability and absorption were assessed by P eff of solutions. P eff of PTX solutions were 1.57E-04 ± 6.84E-05, 3.40E-05 ± 2.90E-05 and 7.56E-05 ± 2.51E-05 for 2.5, 5, and 10 µg/mL concentrations respectively. P eff of PTX + VPL solutions were 3.19E-04 ± 3.62E-06, 3.40E-04 ± 5.81E-05 and 2.36E-04 ± 8.97E-05 for 2.5, 5, and 10 µg/mL concentrations respectively. Repeated measure analysis was used by a general linear model to investigate the difference between PTX and PTX +VPL solutions while the concentration was increased. The difference between P eff of PTX and P eff of PTX + VPL was statistically significant (p = 0.000). Conclusion: PTX has limited intestinal absorption. Increasing the concentration of oral solutions of PTX could not increase its intestinal permeability. VPL could inhibit activity of P-gp. Thus, addition of VPL to PTX could potentially increase intestinal permeability of PTX.