Pharmacokinetics of Lekethromycin in Swine Following Intramuscular Administration at Different Doses with a Single Intravenous Reference Dose for Absolute Bioavailability and Matrix Comparison

Lekethromycin (LKMS) is a novel macrolide veterinary antimicrobial. Its propensity for intracellular accumulation causes discrepancies between whole blood and plasma concentrations, complicating pharmacokinetic evaluations. This study compared the pharmacokinetic characteristics, dose proportionality, and bioavailability of LKMS in whole blood and plasma following intramuscular administration in pigs. Forty-two healthy pigs received LKMS via a single intravenous reference dose (5 mg/kg) for absolute bioavailability estimation or intramuscular (1, 2.5, 5, and 10 mg/kg) injection. Pharmacokinetic parameters were calculated using non-compartmental analysis, and dose proportionality was evaluated via a power model. LKMS exhibited rapid absorption and slow elimination, with a plasma half-life of 49.25 to 67.63 h. Whole blood exposure and peak concentrations were 1.5 to 3 times higher than in plasma, indicating extensive blood cell partitioning. As the intramuscular dose increased, the whole blood-to-plasma concentration ratio decreased from 2.83 to 1.15, suggesting a saturable cell uptake mechanism. Consequently, LKMS exhibited non-linear pharmacokinetics in whole blood but demonstrated linear, dose-proportional pharmacokinetics in plasma. Absolute bioavailability based on plasma ranged from 83.2% to 119.5%. Due to saturable blood cell binding, plasma is the optimal matrix for accurately evaluating LKMS systemic exposure and bioavailability in swine.