Pharmacokinetic and Dynamic Studies on Difloxacin in Goats

Summary:-The present work was conducted to investigate the pharmacokinetic and pharmacodynamic correlation following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of difloxacin in goats. Another goal was to study the sideI. Pharmacokinetics studies :The pharmacokinetics of difloxacin was studied in three-periods cross over design (2X2X2). Drug concentrations in plasma was determined by a microbiological (agar diffusion) assay using E.coli ATCC 25922 as a test organism.Following a single intravenous injection of difloxacin in goats , the plasma concentration-time data were best fitted to a two- compartment open model and the drug was detected in plasma for 24 h. post injection with a mean value of 0.3 ug/ml.Difloxacin was distributed rapidly with half life of distribution (t0.5α ) of 0.34 h. The volume of central compartment (Vc) was 0.43 L/kg. and the volume of distribution at steady state (Vdss) was 2.7 L/kg. Drug was eliminated slowly with half life valueFollowing subcutanous injection of difloxacin in goats , the plasma concentration-time data were best fitted using one- compartment open model and the drug was detected in plasma for 24 h. post injection with a mean value of 0.23 ug/ml.Difloxacin was slowly absorbed by the s.c. route with a half-life of absorption t 0.5 (ab) of 1.62 h .The maximum plasma concentration (Cmax) was 1.57 ug/ml attained 2 h. post administration. The volume of distribution (Vd) was 2.12 L/kg. Elimination halfFollowing intramuscular injection of difloxacin in goats , the plasma concentration-time data were best fitted using one- compartment open model and the drug was not detected in plasma 24 h. post injection in 2 animals.Difloxacin was rapidly absorbed by the i.m. route with a half-life of absorption t 0.5 (ab) of 0.52 h and the Cmax was 0.87 ug/ml achieved 1 h. post injection. The volume of distribution (Vd) was 2.8 L/kg., elimination half life was 10.74 h. and total bodSerum Creatine Kinase (CK) level increased significantly following I.M. injection of difloxacin and returned to normal level one week post administration.The maximum plasma concentration and systemic bioavailabilityof difloxacin following subcutaneous injection were significantly higher compared with those following i.m. injection.Using the surrogate marker Cmax/MIC90 = 8, diflocain could be effective by S.C. route at 5 mg/Kg against bacterial isolates with MIC < 0.2 ug/ml whereas it could be effective by i.m. route at 5 mg/Kgb.wt. against bacterial isolates with MIC < 0.11 ug/ml.Using the surrogate marker AUC24/MIC90= 100, difloxacin would have success against micro-organisms with MIC < 0.17 and 0.09 ug/ml by s.c and i.m. administration, respectively.protein binding tendency of difloxacin in goat plasma was 14.93 % demonstrating low binding capacity of the drug .II- Side effects of difloxacin following repeated injection:Clinically, no adverse effects were observed after administration of difloxacin in goats.Administration of difloxacin (5mg/Kg.bwt.) in goats produced significant increase in AST serum level on 3rd day, significant decrease in albumin serum level on 1st , 3rd and 7th days post administration of the drug and non significant changes in ALT and tDifloxacin produced reversible significant decrease in R.B.C.s count on 7th and 14th days and significant decrease in Hb.conc. on 7th day with significant increase in MCV on 7th and 14th days post administration of the drug .It displayed also reversible s