Vitamins E and A increase the passing of the P-gp substrate ivermectin into the brain in mice

Bunyamin Tras, Kamil Uney, Tugba Melike Parlak, Oznur Tufan

This study aimed to determine the effect of oral Vitamin A and E administrations at different doses on plasma and brain concentrations of ivermectin in mice. The study was carried out on 174 Swiss Albino male mice aged 8-10 weeks. After leaving 6 mice for method validation, the remaining mice were randomly divided into 7 groups with equal numbers of animals. Mice received ivermectin (0.2 mg/kg, subcutaneous) alone and in combination with low (Vit A; 4,000 IU/kg, Vit E; 35 mg/kg) and high (Vit A; 30,000 IU/kg, Vit E; 500 mg/kg) oral doses of Vit A and E. The plasma and brain concentrations of ivermectin were measured using HPLC-FLD. We determined that high doses of vitamins A and E and their combinations increased the passing ratio of ivermectin into the brain significantly. The high-dose vitamin E and the combination of high-concentration vitamin E and A significantly increased the plasma concentration of ivermectin (P<0.05). The high-dose vitamins E and A and their high-dose combination increased the brain concentration of ivermectin by 3, 2 and 2.7 times, respectively. This research is the first in vivo study to determine the interaction between P-gp substrates and vitamins E and A.