Comparative pharmacokinetics and bioequivalence of nine oral ivermectin formulations in dogs

초록

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 (Cmax) and area under the plasma concentration–time curve (AUC72h), 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 (Cmax = 6.07–7.59 ng/mL) varied among formulations. Formulation C showed prolonged elimination (14.97 h) and higher exposure (AUC72h = 214.16 ng·h/mL), whereas formulation H exhibited faster absorption but lower exposure (AUC72h = 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.

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