Comparative pharmacokinetic and bioequivalence of nine oral ivermectin formulations in dogs

Canine heartworm disease remains a major global health issue. Despite the wide availability of ivermectin (IVM) formulations, pharmacokinetic and bioequivalence data are limited.

This study evaluated the pharmacokinetics and bioequivalence of eight oral IVM formulations (B-I) compared with the innovator product (A) in dogs.

Forty-five healthy dogs (mean body weight: 14.3 kg) were divided into nine groups (n = 5). Each received 6.2 µg/kg of IVM orally. Blood samples were collected up to 72 h post-dosing, and plasma IVM concentrations were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were analyzed using a one-compartment model. Bioequivalence was assessed non-compartmentally using 90% confidence intervals for maximum concentration (C_max) and area under the plasma concentration-time curve (AUC_72h), with acceptance limits of 80-125%.

Absorption (Ka = 0.09-0.16 h⁻¹), elimination half-life (T1/2 = 4.89-14.97 h), and systemic exposure (C_max = 6.07-7.59 ng/mL) varied among formulations. Formulation C showed prolonged elimination (14.97 h) and higher exposure (AUC_72h = 214.16 ng·h/mL), whereas formulation H exhibited faster absorption but lower exposure (AUC_72h = 114.36 ng·h/mL). Simulated dosing indicated that most formulations maintained plasma levels above the minimum effective concentration (0.2 ng/mL), except formulation E. Only formulation G met full bioequivalence with the reference product.

All formulations achieved plasma concentrations sufficient for prophylaxis, but only B, C, and G satisfied bioequivalence criteria. Larger sample sizes and standardized evaluation guidelines are recommended for multi-formulation bioequivalence studies.