Pharmacokinetics Of Compound Mebendazole In Crucian Carp(Carassius Auratus)

In this research, A liquid-liquid extraction method was established for the extraction of both mebendazole and levamisole in crucian carp's plasma and tissues with pH11.0 icarbonate buffer and ethyl acetate as the extration reagents.MBZ and LMS concentrations in plasma and tissues were quantitated by means of ion-pair high-performance liquid chromatography (HPLC).Ion-pair reagent was achieved with SDS.Separation was achieved with an Agilent Extend-C18 (250mm×4.6mm,5μm) colunm. A mixture of acetonitrile-ion pair buffer (35:65,v/v) was used as the mobile phase at a flow rate of 1mL/min. Colunm temperature was maintained at 40℃and the UV detection wavelength was set at 220nm. The recovery of MBZ in plasma and tissues was higher than 75.08%, the intra-day and inter-day coefficients of variation were less than 4.83% and 8.98%, respectively. The recovery of LMS in plasma and tissues was higher than 70.90%, the intra-day and inter-day coefficients of LMS were less than 5.63% and 10.38%,respectively. For both MBZ and LMS the correlation of calibration curve were all good, which correlation coefficient were all more than 0.9990.The limit of quantification (LOQ) for both MBZ and LMS were all 0.05μg/mL or 0.05μg/g in plasma and tissues.Carassius auratus were administered orally with a single dosage of 15mg/kg body weight of compound mebendazole (mebendazole:levamisole=4:1)in the pharmacokinetics group.The result showed that the plasma concentration-time data of MBZ and LMS conformed to one-compartment open model with 1st order absorption, the curve of concentration-time were C=13.39(e-0.07t-e-0.17t) and C=4.42(e-0.09t-e-0.28t), respectively. The absorption half-life (t1/2Ka) of MBZ was 4.04h, the elimination half-life (t1/2p) was 10.15h, the area under the serum concentration-time curve (AUC)was 118.11μg·h/mL.The total clearance (CLb) was estimated to be 0.10L/(kg·h).The time-point of maximum plasma concentration of the drug (Tmax) and the maximum plasma concentration (Cmax) were calculated as 8.92h and 4.39μg/mL, The t1/2Ka of LMS was 2.50h, t1/2βwas 7.40h, AUC was 31.20μg·h/mL, CLb was estimated to be 0.10L/(kg·h),Tmax and Cmax were calculated as 5.91h and 1.68μg/mL.The pharmacokinetics of tissues revealed that MBZ and LMS penetrating the organizations easily, such as blood-brain barrier, the fastest absorption is in liver, the slowest elimination is in skin. With the exception of liver and kidney medicine at the curve in the two-compartment open model, the remaining tissues were in the one-compartment open model.The absorption half-life of MBZ in muscle, skin, brain, liver and kidney were 4.80,3.11,7.05,2.42,4.53h. The elimination half-life were 7.70, 23.14,11.95,17.69,12.49h. The peak time were 8.69,10.40,13.09,5.83,9.84h. The peak concentration were 3.44,3.25,2.64,9.70,3.82μg/g. The area under concentration-time curve were 83.58,148.31,97.36,257.06,116.94μg·h/g. The curve of concentration-time were C=12.26(e-0.09t-e-0.14t),C=5.13(e-0.03t-e-0.22t),C=40.34(e-0.06t-e-0.10t), C=22.09e-0.17t+9.24e-0.04t-31.33e-0.29, C=3.97e-0.10t+8.85e-0.06t-12.82e-0.15t,The absorption half-life of LMS in muscle, skin, brain, liver and kidney were 2.62,2.53,4.25,2.75,2.57h. The elimination half-life were 8.61,17.01,9.30,12.76,13.12h.The peak time were 6.46, 8.16,8.85,5.65,6.39h. The peak concentration were 1.16,1.31,0.93,3.29,2.57μg/g.The area under concentration-time curve were 24.24,44.67,24.13,68.93,59.76μg·h/g.The curve of concentration-time were C=2.81(e-0.08t-e-0.26t),C=2.14(e-0.04t-e-0.27t), C=3.31(e-0.07t-e-0.16t), C=13.53e-0.17t+2.98e-0.05t-16.51e-0.25t,C=3.84e-0.12t +2.82e-0.05t-6.66e-0.27t.