Pharmacokinetics And Residues Of Fenbendazole And Its Metabolites In Crucian Carp (Carassius Auratus) At Different Temperatures

Pharmacokinetics and residue of fenbendazole (FBZ) and its metabolites in crucian carp(Carassius auratus) were studied at the water temperature conditions of 10 and 25℃.FBZ and its metabolites concentrations in plasma and tissues were analyzed after liquid-liquid extraction sample pretreatment steps using high-performance liquid chromatography. The correlation of calibration curves which correlation coeffcients (r) were above 0.9990,were all good. This method is accurate and the average recoveries were above 80%in plasma, liver, muscle, kidney and skin.The method had a good precision. The intra-day and inter-day coefficients of variation were less than 10%and 15%, respectively. The limits of detection (LOD) of the three were 0.02μg/mL, 0.03μg/g,0.03μg/g,0.03μg/g and 0.03μg/g in plasma, muscle, liver, skin and kidney, respectively. The limits of quantitation (LOQ) of the three were 0.025μg/mL,0.06μg/g, 0.06μg/g,0.06μg/g and 0.06μg/g in the corresponding tissues, respectively.Fish were administered orally with a single dosage of 10mg/kg body weight of fenbendazole at the water temperatures of 10 and 25℃after the pharmacokinetics study. The results indicated that water temperature affected the pharmacokinetic characteristics of FBZ and ofendazole (OFZ) in crucian carp equally.It manifested rapid absorption, slow elimination and wide distribution. Fenbenddazole sulfone (FBZSO2) has not been detected all the time. Two different water temperature significantly affected the kinesics process.The plasma concentration-time data of FBZ conformed to two-compartment open models in both two different temperatures. The absorption half-lives (t1/2ka) of FBZ were 4.59 and 1.43h under the temperature conditions of 10 and 25℃, respectively, and the distribution half-lives (t1/2α) were 6.89h at 10℃and 4.2h at 25℃. The maximum plasma concentration (Cmax) and the time of maximum plasma concentration (Tmax) were detected to be 2.67μg/mL and 8.56h under 10℃and 3.75μg/mL and 3.43h at higher temperature. The elimination half-lives (t1/2β) were 29.87 and 30.83h at 10 and 25℃. The distribution volumes (Vd/F) of FBZ were detectded to be 1.75L/kg at lower temperature and 1.56L/kg at the higher one. The total clearances (CLb) were computed as 0.13 and 0.19L/(h-kg) at 10 and 25℃, respectively. The areas under the concentration-time curve (AUC) were 78.18μg·h/mL at 10℃and 53.18μg·h/mL at higher temperature.The plasma concentration-time data of OFZ conformed to one-compartment open models at both temperatures.The absorption rate constant (Ka) of OFZ were 0.04h-1 at 10℃and 0.05 h-1 at 25℃.The elimination half-life (t1/2ke) were 17.05h and 15.27h at 10℃and 25℃. AUCwere14.69μg·h/mL at 10℃and 8.26μg·h/mL at 25℃. CLbof OFZ were calculated as 0.68 and 1.21 L/(h·kg) at 10 and 25℃, and Cmax were estimated to be 0.35 and 0.25μg/mL at 10 and 25℃.Fish were administered in the residue group orally with a dosage of 10mg/kg body weight of fenbendazole. The study showed that water temperature also played an important part in the residue process.The elimination half-lives (t1/2ke) of FBZ and OFZ in all the tissues at 10℃were longer than those at 25℃. The drugs could still be detected at 6d after administration at lower temperature,while they can not be detected after 4d at higher temperature. Comparing with the other tissues, the elimination of FBZ and OFZ in skin was slowest at both two different temperatures.Skin behaved as a reservoir in crucian carp. At last FBZSO2 has not been detected all the time.The pharmacokinetics study showed that after a oral dosage of 10mg/kg body weight in crucian carp, the pharmacokinetic characteristics of FBZ and OFZ equally showed rapid absorption, wide distribution and slow elimination. Water temperature played significantly affected both residue and kinesics processes.After the residue study, the withdrawal periods of FBZ could not be less than 9d at 10℃and 5d at higher temperature.