Effects of vitamins A and E on eprinomectin transport in Caco-2 cells

Eprinomectin (EPR) is a macrocyclic lactone antiparasitic widely used in veterinary medicine. Although the off-label oral use of the pour-on formulation of EPR is known to be effective and practical, data regarding its interactions with foods or vitamin supplements that may affect intestinal absorption remain limited. This study investigated the effects of vitamin A (VA) and vitamin E (VE) on the transepithelial permeability of EPR using the Caco-2 cell monolayer model. An analytical method for EPR quantification was developed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The integrity of tight junction dynamics in epithelial monolayers was monitored using transepithelial electrical resistance (TEER) throughout the 21-day differentiation protocol. Apparent permeability coefficients (P _app) were calculated in both apical-to-basolateral and basolateral-to-apical directions and compared between EPR alone and EPR combined with the vitamins. EPR alone exhibited moderate permeability across Caco-2 monolayers (7.64 ± 2.27 × 10^-6 cm/s). Notably, our results demonstrate that co-treatment of EPR with VA alone, as well as co-treatment with the combination of VA and VE, significantly reduced EPR permeability in vitro (P < 0.001). These findings highlight possible food/nutrient-drug interactions relevant to veterinary oral drug administration, and additional mechanistic and in vivo studies will be necessary to clarify the underlying pathways.