| Pharmacokinetics and residue elimination of Hydrochloric acid albendazole sulfoxide and its metabolites (albendazole sulfone; albendazole-2-aminosulfone) were studied in crucian carp (Carassius auratus) kept at two water temperatures of 10 and 25℃. ABZSO and its metabolites concentrations in plasma and tissues were analyzed by means of reversed-phase high-performance liquid chromatography (RP-HPLC) after liquid-liquid extraction. The correlation of calibration curves were all good, which correlation coefficients (r) were more than 0.9996. The average of albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2), albendazole-2-aminosulfone (ABZ-SO2NH2) extraction recoveries were more than 86% from plasma, and more than 71% from muscle, skin, liver and kidney. The intra-day and inter-day coefficients of variation were less than 6% and 10%.Fish were administered orally with a single dosage of 10mg/kg body weight in the pharmacokinetics group. The results revealed that ABZSO in plasma was significantly higher than that of ABZSO2; ABZ-SO2NH2 was not detected. The pharmacokinetic characteristics of ABZSO and its metabolites in crucian carp manifested rapid absorption, wide distribution and slow elimination. Water temperature played an important role in the kinesics process, at low water temperature the absorption is relatively slower. The plasma concentration-time data conformed to one-compartment open models at both temperatures with ABZSO and ABZSO2. The absorption half-lives (t1/2ka) of ABZSO were found to be 3.86h at 10℃and 1.29h at 25℃, whereas the elimination half-lives (t1/2ke) were 16.34h at 10℃and 6.72h at 25℃. the maximum plasma concentration (Cmax) with 3.20μg/mL and 4.39μg/mL were obtained at 10.58h and 3.80h at 10 and 25℃, compared to ABZSO2 (0.78μg/mL at 12.82h and 1.03μg/mL at 7.04h), respectively. The distribution volumes (Vd/F) of ABZSO were estimated to be 1.99L/kg at 10℃and 1.53L/kg at 25℃. The total clearances of ABZSO (CLb) were computed as 0.08 and 0.19L/(h·kg) at 10 and 25℃, respectively. The areas under the concentration-time curve (AUC) were 118.22μg·h/mL at 10℃and 63.12μg·h/mL at 25℃, Compared to ABZSO2 (28.86 and 20.52μg·h/mL) respectively.After oral administration with a dosage of 10mg/kg body weight, fish were sacrificed at 4,8,12,24,48,60,72,96,120 and 144h after administration and samples of muscle, skin, liver and kidney were collected to determine ABZSO and its metabolites concentrations. The results showed that ABZSO was mainly converted to ABZSO2, concentrations of ABZSO and its mainly metabolite ABZSO2 were detected in muscle, skin, liver and kidney, whereas ABZ-SO2NH2 was only found in liver and kidney. the elimination half-lives (t1/2ke) of ABZSO and its metabolites from all tissues at 10℃were longer than those at 25℃. The drug in all tissues eliminated slowly at both temperatures, which could still be detected at 96h time-point after administration in all tissues. Comparing with the other tissues, the concentrations of ABZSO and its metabolites were highest in skin at this time-point. What's more, skin is the edible products of most fish, the elimination of ABZSO and its metabolites in skin was slowest, which behaved as a reservoir in crucian carp.Based on the results of the residue study, the withdrawal periods should not be less than 17d at 10℃and 10d at 25℃when administered orally with a single dosage of 10mg/kg body weight. |
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