Pharmacokinetics of Doramectin After Subcutaneous and Intramuscular Administrations in Siamese Freshwater Crocodiles (Crocodylus siamensis)

Doramectin (DRM) is a broad-spectrum macrocyclic lactone antiparasitic agent widely used in veterinary medicine. Its pharmacokinetics in reptiles, particularly Siamese freshwater crocodiles (Crocodylus siamensis), remain limited. This study aimed to characterize the pharmacokinetic profiles of DRM following subcutaneous (SC) and intramuscular (IM) administration in Siamese crocodiles. Twenty clinically healthy male crocodiles were randomly allocated into four groups (n = 5 per group) and administered a single dose of DRM at 0.2 or 0.3 mg/kg body weight (b.w.) via either the SC or IM route. Blood samples were collected from pre-dose to 60 days after administration, and plasma DRM concentrations were quantified using a validated high-performance liquid chromatography method with fluorescence detector. Pharmacokinetic parameters were determined by non-compartmental analysis. Plasma DRM concentrations remained quantifiable through day 60 in 19 of 20 animals. Geometric mean maximum plasma concentrations (Cmax) were 14.73 and 20.28 ng/mL following SC administration at 0.2 and 0.3 mg/kg, respectively, and 24.48 and 36.34 ng/mL following IM administration. Significantly higher Cmax values were observed at 0.3 mg/kg for both routes (p < 0.05). Median Tmax values were 11 and 9 days following SC administration and 3 and 4 days following IM administration at 0.2 and 0.3 mg/kg, respectively. The geometric mean terminal elimination half-lives (T1/2λz) were 5.37 and 9.73 days for SC administration and 7.38 and 9.97 days for IM administration at 0.2 and 0.3 mg/kg, respectively. Systemic exposure increased with dose. The geometric mean AUC0–last increased numerically from 368.84 to 491.87 ng × day/mL following SC administration and significantly from 372.45 to 643.97 ng × day/mL following IM administration (p < 0.05). Intramuscular administration resulted in higher Cmax and more rapid attainment of peak plasma concentrations than SC administration. These findings demonstrate prolonged systemic persistence and dose-related pharmacokinetic changes in DRM in freshwater crocodiles and provide species-specific information to support further evaluation of dosage regimens.