The Pharmacokinetics of Doxycycline in Channel Catfish (Ictalurus punctatus) Following Intravenous and Oral Administrations

The objective of this study was to investigate the bioavailability (BA) and pharmacokinetics (PK) of doxycycline (DC) in channel catfish (Ictalurus punctatus) following a single intravenous injection at 5 mg/kg and a single oral administration at 50 mg/kg at 24 ℃. The calculation of PK parameters was based on the software of 3P97. The plasma samples were determined using the ultra-performance liquid chromatography. Following oral administration, the multiple-peak phenomenon presented in concentration vs. time curve of DC at 2 h (107.01 mg/L), 8 h (55.07 mg/L), and 72 h (15.10 mg/L), respectively. The compartmental model can’t simulate the oral concentration vs. time profile beside a non-compartmental model. The calculated parameters of the elimination rate constant (λz), the elimination half-life (t1/2λz), and the area under concentration vs. time curve (AUC0-144) were 0.037 1/h, 18.91 h, and 2255.45 µg.h/mL, respectively. After intravenous administration, the concentration vs. time profile of DC was best described by a two-compartmental open model without absorption. The parameters of the distribution rate constant (α), the distribution half-life (t1/2), the elimination rate constant (β), the elimination half-life (t1/2β), the apparent distribution volume at steady state (Vss), the total clearance (Cl) and the area under concentration vs. time curve (AUC0-∞) were 2.79 1/h, 0.25 h, 0.042 1/h, 16.51 h, 300.00 mL/kg, 14.00 mL/h/kg, and 364.99 μg.h/mL, respectively. For the calculation of BA values at the same condition, the data obtained from intravenous injection were also iterated based on a non-compartmental model, and the corresponding parameters of λz, t1/2λz, Vz, Cl, and AUC0-144 were 0.019 1/h, 36.26 h, 480.00 mL/kg, 9.10 mL/h/kg, and 514.45 µg.h/mL, respectively. However, there was a considerable difference in the same parameter calculated by compartmental and non-compartmental approaches. Finally, a medium BA value of DC was evaluated to be 43.84%. This study will provide a framework for determining the BA of DC in the development of a new formulation in the future, and provide some information for the appropriate usage of DC in aquaculture.