Tramadol Effects on Lameness Score After Inhibition of P-GP by Ivermectin Administration in Horses: Preliminary Results

This study aimed to evaluate the effects and lameness degree in horses administered tramadol after the P-glycoprotein (P-gp) enteric inhibitor ivermectin. Six horses were randomly distributed into three groups, which received two different doses of tramadol by a nasogastric tube: 1 mg/kg (tramadol group 1(GT1)), 4 mg/kg (tramadol group 4 (GT4)), and tramadol 1 mg/kg combined with ivermectin 0.2 mg/kg PO (ivermectin tramadol group (GT1 + Ive)), with one-week washout interval. Heart rate (HR), respiratory rate (RR), intestinal motility, body temperature, and the degree of lameness were evaluated for 360 minutes. The blood gas parameters were evaluated at 0, 60 minutes, and 120 minutes. There were no differences in HR and the degree of lameness. Hypomotility occurred in GT1 and GT4 only at the end of the evaluation period, and RR increased in all groups. We conclude that inhibition of enteric P-gp by ivermectin did not alter the effects of tramadol, suggesting that tramadol is not a substrate for P-gp. However, future studies should be conducted to assess the interaction between P-gp inhibitors on the pharmacokinetics of tramadol.