Pharmacokinetic Of Enrofloxacin Lactate Soluble Powder And Residues Depletion Of Different Enrofloxacin Salt Preparation In Broilers

Enrofloxacin is the third generation fluoroquinolone with broad antimicrobial spectrum and high bactericidal activity which was developed exclusively for veterinary use.And it has no cross-resistance with other antimicrobial agents.Enrofloxacin showed favourable pharmacokinetic properties such as excellent bioavailability, large volume of distribution. However, enrofloxacin slightly soluble in water. Enrofloxacin lactate, enrofloxacin sodium and enrofloxacin hydrochloride as water-soluble powders provides a great convenience for clinical medication. The tests on the residues depletion of three kinds of enrofloxacin soluble powders in broiler tissues provided the theory basis for the withdrawal time to ensure the safety and security of human health and animal products in the international market competition.1. Pharmacokinetic study of enrofloxacin lactate soluble powder in broilersThe pharmacokinetics and bioavailability of enrofloxacin lactate were investigated in24healthy Shuqinhuang Chicken. Enrofloxacin lactate was administered intravenously (i.v.) and orally (p.o.) at a dose10mg/kg body weight(clinically recommend dose). The concentrations of enrofloxacin lactate in plasma were determined by high-performance liquid chromatography (HPLC).Pharmacokinetic analysis of plasma concentration-time data after single i.v. and p.o. administration were performed with the pharmacokinetic computer program3p87. Following intravenous administration, the drug concentration-time graph was characteristic of a two-compartment open model, The main pharmacokinetic parameters of enrofloxacin lactate:t1/2a (0.45±0.16) h, t1/2β (7.02±1.42) h, CL(s)(0.38±0.10) mg/kg/h, AUC (23.69±5.56)(mg/L)×h.The results showed that the concentration-time data of enrofloxacin in plasma after oral administration are fitted to a two-compartment open model. The main pharmacokinetic parameters:t1/2ka (0.60±0.01)h, t1/2kc (8.25±1.73)h, tpeak (2.44±0.17) h, Cmax (1.44±0.30) mg/L, AUC (20.74±3.80)(mg/L)×h, F87.54%. Enrofloxacin concentrations in plasma after the drug administration showed that a rapid distribution phase was followed by the slower elimination phase in broilers. The bioavailability was high by the oral routes.2. Determination of enrofloxacin residues in broiler tissues by high performance liquid chromatographySamples of muscle, liver and kidney were thawed and homogenated.The phosphate-buffered saline were added to the samples and vortexed and centrifuged. The supernatant was concentrated and purificated by C18column solid phase extraction. The liquid was filtered through0.45μm disposable syringe filters prior to analysis by HPLC system. Chromatographic analyses were carried out on a reversed-phase liquid chromatography systerm with fluorescence detector with excitation wave length of280nm and emission wave length of450nm.The straight line established by standard addition was used as the quantitative standard curve for determination of enrofloxacin and ciprofloxacin by HPLC. The results showed that the linear range was0.01-1.0μg/mL and correlation coefficients were more than0.999. The detection limit for broilers tissues was0.01mg/kg. The enrofloxacin and ciprofloxacin were analyzed in spiked samples of three kinds of chicken tissues with mean recoveries in the range of74-1%-86-8%at spiked levels of0.05、0.1、1mg/kg. The relative standard deviations of CV of within group, the CV between groups were no more than10%and7%,respectively. The method is sufficient for routine residue analysis.3. Comparison of residues depletion of different enrofloxacin salt preparation in broiler tissuesThe study was performed in35,40-day-old, healthy Shuqinhuang Chicken, weighing1.5±0.2kg body weight. They were administered three kinds of enrofloxacin soluble powders p.o. once per day at a dose of100mg/L for seven successive days,respectively. Five broilers per day were slaughtered at0,1,3,5,7,9,11days after the last administration. The residues of enrofloxacin and its active metabolite ciprofloxacin were extracted from the homogenized tissue with phosphate-buffered saline and they were determined by high performance liquid chromatography.3.1The residue elimination of enrofloxacin lactate soluble powder:Enrofloxacin concentrations in muscle,liver and kidney were(1.899±0.922) mg/kg,(2.574±1.171) mg/kg and (0.967±0.624) mg/kg respectively at zero withdrawal time. The muscle, liver and kidney tissue residues of enrofloxacin decreased to less than MRL after5d,7d and3d of withdrawal time, respectively.The raw data were analysed with WT1.4program. Results showed that the withdrawal time of enrofloxacin lactate in broilers was at least8d.3.2The residue elimination of enrofloxacin sodium soluble powder:Enrofloxacin concentrations in muscle,liver and kidney were (1.253±0.319) mg/kg,(2.024±0.902) mg/kg and (0.576±0.099) mg/kg respectively at zero withdrawal time. The muscle, liver and kidney tissue residues of enrofloxacin decreased to less than MRL after3d,5d and Id of withdrawal time,respectively.The raw data were analysed with WT1.4program. Results showed that the withdrawal time of enrofloxacin sodium in broilers was at least5d.3.3The residue elimination of enrofloxacin hydrochloride soluble powder:Enrofloxacin concentrations in muscle, liver and kidney were (8.038±2.074) mg/kg,(12.678±3.667)mg/kg and (3.273±0.879)mg/kg respectively at zero withdrawal time. The residues of enrofloxacin have not been detected in the tissues of broiler after9d of withdrawal time.The raw data were analysed with WT1.4program. Results showed that the withdrawal time of enrofloxacin hydrochloride in broilers was at least10d. The results showed that residue concentrations in the tissues found in all examined tissues were liver> muscle> kidney for kidney at zero withdrawal time. The liver had the slowest elimination. The withdrawal time of enrofloxacin lactate,enrofloxacin sodium and enrofloxacin hydrochloride in broilers was8d,5d and10d respectively.The withdrawal time of enrofloxacin in broilers was8d in the bulletin NO.278issued by the Ministry of Agriculture.Thus, different enrofloxacin soluble powder and enrofloxacin in broilers have some differences in the process of elimination and the withdrawal time is also slightly different.