Pharmacokinetics and Tissue Distribution of Albendazole and Its Three Metabolites in Yellow River Carp (Cyprinus carpio haematopterus) after Single Oral Administration

Abstract

This study aimed to evaluate the pharmacokinetics and tissue distribution of albendazole (ABZ) and its three metabolites─albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO₂), and albendazole-2-aminosulfone (ABZ-2-NH₂–SO₂)─in Yellow River carp (Cyprinus carpio haematopterus) reared at 17.2 ± 1.1 °C after single oral administration of 12 mg/kg body weight (BW) ABZ. The concentrations of ABZ and its metabolites in different samples were measured using high performance liquid chromatography (HPLC). Pharmacokinetic parameters for ABZSO₂ and ABZ-2-NH₂–SO₂ were not estimated due to their low levels. Pharmacokinetic analysis of ABZ and ABZSO was conducted using average concentration–time data with Phoenix software. The C_max values (μg/mL or μg/g) of ABZ in skin-on muscle, plasma, bile, kidney, gills, liver, and intestine were 0.65, 0.70, 1.01, 1.61, 1.71, 2.42, and 3.34, respectively. The elimination half-life (t_1/2λZ) of ABZ was longest in skin-on muscle (37.92 h), followed by the liver (32.07 h), gills (31.92 h), bile (31.51 h), kidney (26.96 h), intestine (20.81 h), and plasma (19.86 h). For ABZSO, the C_max values (μg/mL or μg/g) in plasma, skin-on muscle, gills, intestine, liver, kidney, and bile were 0.46, 0.76, 0.89, 1.13, 1.54, 1.89, and 3.78, respectively. These findings indicate that ABZ and ABZSO are widely distributed and metabolized slowly in Yellow River carp after single oral administration. The higher ABZ concentrations in the liver and kidney suggest that these are the main metabolic organs for ABZ, while the elevated levels of ABZSO in bile indicate that bile excretion is the main pathway of ABZSO elimination. Based on the marker residue (ABZ-2-NH₂–SO₂) and its maximum residue limit (MRL) of 0.1 μg/g in skin-on muscle recommended by China, no withdrawal period was required for ABZ in Yellow River carp after a single oral dose of 12 mg/kg BW. However, using the marker residue (the sum of ABZ and its three metabolites) and the MRL of 0.1 μg/g for ruminants recommended by the EU, the withdrawal period was calculated to be 7 days or 118 °C-day under the same dosing regimen.