| Pharmacokinetics and regularity of distribution of ampicillin (AMP) and sulbactam pivoxyl (SUL pivoxil) were studied in chickens following oral administration. The concentrations of these two drugs in plasma and tissues were analyzed using high-performance liquid chromatography after liquid-liquid extraction sample pretreatment steps. A mixture of acetonitrile-phosphate buffer (3:97, v/v) was used as the mobile phase at a flow rate of1mL/min. Column temperature was maintained at35℃and the UV detection wavelength was set at210nm. Calibration curves were established under this condition, correlation coefficients (r) were all above0.9990. The average extraction recoveries of AMP were above92%in plasma,68%in muscle, lung, liver and kidney, of SUL, were above88%in plasma,71%in muscle, lung, liver and kidney. The precision of this method was proved well enough, with a low intra-day and inter-day coefficients of variation less than10%. The limits of detection (LOD) of ampicillin were0.025μg/mL0.05μg/g,0.05μg/g,0.0625μg/g and0.05μg/g in plasma, muscle, lung, liver and kidney, respectively. The limits of quantitation (LOQ) were0.05μg/mL,0.075μg/g,0.075μg/g,0.10μg/g and0.075μg/g in the corresponding tissues, respectively. The limits of detection (LOD) of sulbactam were0.025μg/mL,0.05μg/g,0.0625μg/g,0.05μg/g and0.05μg/g in plasma, muscle, lung, liver and kidney, respectively. The limits of quantitation (LOQ) were0.05μg/mL,0.075μg/g,0.10μg/g,0.075μg/g and0.075μg/g in corresponding tissues, respectively.After orally administered AMP and SUL pivoxil (4:1) with the dosage of20mg/kg·B·W, we studied the pharmacokinetics of these two drugs. The results manifested that AMP and SUL were both absorbed rapidly, distributed widely and had short elimination half-lives. The plasma concentration-time data of AMP conformed to one-compartment open model, while SUL to two-compartment open models. Pharmacokinetic equations of these two drugs were C=2.78(e-0.48t-e-1.76t), C=7.82e-1.90t+0.64e-0.23t-8.46e-3.14t respectively. The absorption half-lives, the elimination half-lives, the maximum plasma concentrations (Cmax), the time of maximum plasma concentrations (Tmax), the total clearances (CLb), the areas under the concentration-time curve (AUC), the distribution volumes (Vd/F) of AMP and SUL were0.39and0.37h,1.44 and3.06h,1.24and1.85μg/mL,1.02and0.45h,4.21and4.26μg·h/mL,3.80and0.94L/(h·kg),7.92and1.08L/kg, respectively. The bioavailability (F) of sulbactam pivoxil was69.49%.The study of distribution revealed that ampicillin and sulbactam in penetrating the organizations ability to absorb quickly and eliminate slowly. The tissue concentration-time data of AMP and SUL, with the exception of muscle in a single-compartment model of absorption, the remaining was in two-compartment model. The curve of ampicillin and sulbactam’s concentration-time in muscle, liver, kidney and lung were C1=1.55(e-0.04t-e-0.49t), C2=9.66e-0.19t+1.70e-0.03t-11.36e-0.43t, C3=8.46e-0.19t+0.84e-0.02t-9.30e-0.41t, C4=6.40e-0.17t+0.73e-0.02t-7.13e-0.53t, C5=2.38(e-0.05t-e-0.87t), C6=9.73e-0.29t+1.95e-0.02t-11.68e-0.52t, C7=11.21e-0.33t+1.60e-0.03t-12.81e-0.56t, C8=3.63e-0.33t+2.79e-0.05t-7.42e-0.72t... |
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