Pharmacokinetics and plasma protein binding of tenvermectin in rats administered subcutaneously and intravenously with the injectable formulation

Tenvermectin (TVM), a novel avermectin antiparasitic candidate, still lacks comprehensive data regarding its pharmacokinetics and plasma protein binding. Owing to its low water solubility and the unavailability of commercial formulations, a laboratory-made injectable preparation was developed for preclinical pharmacokinetic testing. We determined the pharmacokinetic profiles, dose proportionality, and plasma protein binding of TVM in rats injected with this experimental formulation. The pharmacokinetic profiles and plasma protein binding of TVM were evaluated in rats after subcutaneous administration at 0.5, 1.25, and 2.5 mg/kg body weight (BW) and intravenous administration at 1.25 mg/kg BW of the experimental injectable formulation, with plasma protein binding assessed by equilibrium dialysis. Following subcutaneous administration, TVM reached peak plasma concentrations at 4–7 h and exhibited an elimination half-life of approximately 9–12 h. Over the tested subcutaneous dose range, the power model analysis confirmed that systemic exposure rose with increasing dose. The prespecified slope criterion was met for C max but narrowly not met for AUC 0–t . After intravenous administration at 1.25 mg/kg BW, the AUC 0−∞ was 1925.50 h·ng/mL. In the dose-matched comparison, the estimated absolute bioavailability after subcutaneous administration was approximately 76% (95% CI: 63.64%-91.61%). In rat plasma, the apparent protein binding rates of TVM at 50, 100, and 200 ng/mL were 69.37 ± 5.62%, 72.86 ± 2.97%, and 72.51 ± 2.45%, respectively, with no significant concentration dependence. Together, these findings indicate that injectable TVM exhibits systemic exposure after subcutaneous administration, approximately dose-proportional pharmacokinetics within the tested range, and moderate apparent plasma protein binding in rats. These data provide preclinical pharmacokinetic evidence to support the further evaluation and veterinary development of TVM as a novel antiparasitic agent.