Abstract
IMPORTANCE: Canine heartworm disease remains a major global health issue. Despite the wide availability of ivermectin (IVM) formulations, pharmacokinetic and bioequivalence data are limited. OBJECTIVE: This study evaluated the pharmacokinetics and bioequivalence of eight oral IVM formulations (B-I) compared with the innovator product (A) in dogs. METHODS: 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%. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.