Effects of verapamil on the pharmacokinetics of ivermectin in rabbits

This study was aimed to investigate the influence of verapamil-mediated inhibition of P-glycoprotein (P-gp) on the pharmacokinetics of ivermectin (IVM) given orally and subcutaneously (SC) to rabbits. Twenty New Zealand rabbits were allotted to 4 groups (n = 5) and received IVM either orally or SC (0.4 mg/kg) alone or co-administered with verapamil (2 mg/kg SC, 3 times at a 12-hr interval). Plasma, fecal, and urine samples were collected over 30 days after medication to assess IVM concentrations in these samples. No significant differences were observed in the pharmacokinetic parameters of IVM between oral and SC administrations. The area under the plasma concentration-time curve was higher (p < .05) after IVM (oral)/verapamil treatment, compared with oral IVM alone. Moreover, the time to the C_max of IVM was shorter (p < .05), whereas the elimination half-life and the mean residence time were longer (p < .05) in the presence of verapamil. The IVM/verapamil combination administered orally or SC reduced fecal IVM concentrations, compared with IVM alone. In conclusion, the significant changes by verapamil on the pharmacokinetics of IVM, likely due to the inhibition of a P-gp-mediated intestinal secretion, may change IVM's antinematodal activity.