Depletion of Albendazole and Its Metabolites and Their Impact on the Gut Microbial Community Following Multiple Oral Dosing in Yellow River Carp (Cyprinus carpio haematopterus)

Healthy Yellow River carp (Cyprinus carpio haematopterus) reared at a water temperature of 23 ± 0.6 °C were orally administered albendazole (ABZ) at a dose of 12 mg/kg body weight (BW) once daily for seven consecutive days. At predetermined time points after the final administration, five fish were randomly selected for sampling. Plasma, skin-on-muscle, liver, and kidney tissues were collected, and the concentrations of ABZ and its three metabolites—albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2), and albendazole-2-aminosulfone (ABZ-2-NH2−SO2)—were determined using high-performance liquid chromatography (HPLC). The results indicated that ABZ and ABZSO were widely distributed across tissues, while ABZSO2 and ABZ-2-NH2-SO2 were only present at trace levels. Pharmacokinetic analysis of ABZ and ABZSO in plasma and tissues was performed using noncompartmental analysis (NCA). ABZ peaked in plasma at 0.73 μg/mL at 24 h after the last administration, with an elimination half-life (t1/2λZ) of 38.56 h. ABZSO reached a peak plasma concentration of 1.54 μg/mL at 24 h, with a t1/2λZ of 53.73 h. According to China’s national standard, where ABZ-2-NH2−SO2 is the marker residue with a maximum residue limit (MRL) of 100 μg/kg in fish skin-on muscle, no withdrawal period was necessary. However, based on the European Union standard—which uses the sum of ABZ and its three metabolites as the marker residue and an MRL of 100 μg/kg in ruminants—a withdrawal period of 16 days (or 351 °C-days) was required. Additionally, the study assessed changes in the intestinal microbiota following multiple oral doses of ABZ. The results indicated that ABZ administration significantly altered microbial diversity and composition in a dose- and time-dependent manner. After drug withdrawal, the intestinal microbiota gradually returned to baseline levels, similar to the untreated control group.