Pharmacokinetics Of Enrofloxacin Coating Preparation Following Oral Administration In Pigs

The content,encapsulation efficiency,in vitro release rate and stability of enrofloxacin coating preparation were study using the following chromatographic method for testing. Separation was achieved with an Agilent TC-C18(4.6×150 mm,5μm) colunm.A mixture of acetonitrile-5 g/L citric acid-triethylamine(160:840:2,v/v/v) was used as the mobile phase with the flow rate at 1mL/min.Colunm temperature was maintained at 40℃and the UV detection wavelength was set at 278 nm.The method was stable with a good linearity and reproducibility.Based on the above studies,pharmacokinetics of enrofloxacin coating preparation in pig given the preparation alone and in combination with probenecid was studied to evaluate its controlled releasing effect and the effect of probenecid on the elimination of enrofloxacin and ciprofloxacin in pigs.A liquid liquid extraction method was established for the extraction of both enrofloxacin and ciprofloxacin in pig plasma with acetonitrile and glacial acetic acid as the extration reagents.The chromatographic condition developed by Intorre L et al.with slight modifications was adopted for simultaneous detection of both enrofloxacin and ciprofloxacin in pig plasma.Separation was achieved with an Agilent TC-C18(4.6×150mm,5μm) colunm.A mixture of acetonitrile-phosphate buffer(pH3)(12:88,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 278 nm.For both enrofloxacin and ciprofloxacin,the assay was linear between 0.05 and 5μg/mL,with a correlation coefficient of 0.9995 and 0.9996 respectively.The limit of quantification(LOQ) for both enrofloxacin and ciprofloxacin was 0.05μg/mL and the recovery of enrofloxacin and ciprofloxacin in plasma was higher than 84.02±6.48%and 78.97±6.01%respectively.Intra-day and inter-day coefficients of variations for enrofloxacin were between 4.00%and 7.71%and these numbers for ciprofloxacin were between 1.72%and 10.16%.The extraction and detection methods were stable with excellent reproducibility and a good correlation coefficient and recovery for both enrofloxacin and ciprofloxacin.Eighteen pigs were randomly divided into three group,given enrofloxacin alone,enrofloxacin coating preparation alone and enrofloxacin coating preparation together with probenecid.Following a single oral dose of enrofloxacin at 10 mg/kg bodyweight,enrofloxacin coating preparation at 10 mg/kg bodyweight(calculated as enrofloxacin) and probenecid at 40 mg/kg bodyweight,the drug concentration-time data of all the three groups matched two compartment open model very well.For the group receiving enrofloxacin coating preparation alone,the absorption half-life(t_1/2ka), distribution half-life(t_1/2α) and elimination half-life(t_1/2β) of enrofloxacin lengthened significantly from 0.67±0.18 h to 1.07±0.19 h,1.33±0.10 h to 3.34±0.19 h and 7.21±1.24 h to 16.06±2.35 h respectively compared with the group receiving enrofloxacin alone. Area under the plasma concentration-time curve(AUC) also increased significantly from 18.80±2.50μg.h/mL to 41.83±5.11μg.h/mL.These changes in pharmacokinetic parameters showed that a significant controlled releasing effect has been successfully achieved for enrofloxacin coating preparation.The co-administration of probenecid with enrofloxacin coating preparation resulted a slight increase of t_1/2β and AUC for both enrofloxacin and ciprofloxacin.The value of t_1/2β for enrofloxacin and ciprofloxacin lengthened from 16.06±2.35 h to 18.02±2.52 h and 19.92±2.65 h to 25.71±3.94 h respectively and AUC increased from 41.83±5.11μg.h/mL to 49.97±6.44μg.h/mL and 6.27±0.92μg.h/mL to 9.36±1.05μg.h/mL respectively compared with the group receiving enrofloxcacin coating preparation alone,showing that probenecid could lengthened the elimination of both enrofloxacin and ciprofloxacin in pigs.As probenecid prolongs the eliminnation half-life of quinolones only by decreasing the renal tubular secretion of the drugs,according to the degree of increase of the parameters,it can be concluded that only a limited amount of enrofloxacin and ciprofloxacin was eliminnated through renal tubular secretion.