Pharmacokinetics and tissue residues of hydrochloric acid albendazole sulfoxide and its metabolites in crucian carp (Carassius auratus) after oral administration

The pharmacokinetics and residues elimination of hydrochloric acid albendazole sulfoxide (ABZSO) and its metabolites were studied in healthy crucian carp (Carassius auratus, 250 ± 30 g) kept at water temperatures of 10 °C and 25 °C. The concentrations of ABZSO and its metabolites concentration in plasma and tissues were determined using high-performance liquid chromatography (HPLC) using an ultraviolet detector. The results revealed that the plasma concentration of ABZSO in plasma was significantly higher than that of albendazole sulfone (ABZSO2), whereas Albendazole-2-aminosulfone (ABZ-SO2NH2) was not detected. The plasma concentrations of ABZSO and its main metabolite ABZSO2 concentration–time data were fitted using a single-compartment model at 10 °C and 25 °C. The absorption half-life (t1/2 kat1/2 ka) of ABZSO was 3.86 h at 10 °C and 1.29 h at 25 °C, whereas the elimination half-life (t1/2 ket1/2 ke) was 16.34 h at 10 °C and 6.72 h at 25 °C; the maximum plasma concentration (Cmax) and the time-point of maximum plasma concentration (Tp) were calculated as 3.20 μg mL−1 and 10.58 h at 10 °C, 4.39 μg mL−1 and 3.80 h at 25 °C. The distribution volume (Vd/F) of ABZSO was estimated to be 1.99 L kg−1 at 10 °C and 1.53 L kg−1 at 25 °C; the total body clearance (CLb) of ABZSO were computed as 0.08 and 0.19 L/(h kg) at 10 and 25 °C, respectively; the areas under the concentration–time curve (AUC) was 118.22 μg mL−1 h at 10 °C and 63.12 μg mL−1 h at 25 °C. The t1/2 kat1/2 ka of ABZSO2 was found to be 6.39 °C at 10 °C and 3.73 h at 25 °C, whereas the t1/2 ket1/2 ke was 12.86 h at 10 °C and 6.56 h at 25 °C; the Cmax and Tp of ABZSO2 was calculated as 0.78 μg mL−1 and 12.82 h at 10 °C, 1.03 μg mL−1 and 7.04 h at 25 °C, respectively; the Vd/F of ABZSO2 were estimated to be 6.43 L kg−1 at 10 °C and 4.61 L kg−1 at 25 °C; the CLb of ABZSO2 were computed as 0.34 and 0.49 L/(h kg) at 10 °C and 25 °C, respectively; the AUC of ABZSO2 were 28.86 μg mL−1 h at 10 °C and 20.52 μg mL−1 h at 25 °C. It was demonstrated that ABZSO2 was the main metabolite of ABZSO. The concentrations of ABZSO and its main metabolite (ABZSO2) were detected in muscle, skin, liver and kidney, whereas ABZ-SO2NH2 was only detected in liver and kidney. The ABZSO and it metabolite (ABZSO2) could still be detected at 4 d time-point after administration at both temperatures in all tissues. The results revealed that the depletion of ABZSO and its metabolite (ABZSO2) in crucian carp was slower with a long half-life time, especially at lower water temperature.

► The pharmacokinetics of ABZSO and its metabolites were studied in healthy crucian carp at 10 °C and 25 °C.
► Serve as reference for the dosage regimen.
► Calculate the withdrawal times of the drug in different seasons.
► The elimination of the drug in crucian carp was largely influenced by water temperature.