Comparasion of Pharmacokinetic Profiles of Some Antimicrobial Agents in Plasma and Lymph Fluids

Some pharmacokinetic parameters and concentrations of four antimicrobial agents in plasma and lymph fluids were compared for determination of penetration into peripheral tissues. Eighteen healthy, adult sheep (Turk Merino x Hampshire cross, 18-24 month, weighing 32-37 kg) were used. For collection of lymph samples, the efferent vessel of NI, cervicalis superficialis sinister was cannulated with a polyethylene catheter. All antimicrobial agents were administered intramuscularly at single recommended doses (Chloramphenicol 30 mg/kg b.wt., Enrofloxacin 2.5 mg/kg b. wt., Sulphadoxine-trimethoprim 16 mg/kg b.wt). Subsequently, blood and lymph samples were concurrently obtained at 2, 4, 8, 12, 16 and 24 hr postinjection. Concentrations of these agents in all samples were analysed by HPLC. Concentrations of enrofloxacin in lymph fluids at all sampling times were found to be higher than plasma (p<0.01), but concentrations of sulphadoxine in plasma and lymph fluids at all sampling times were not found to be statistically different (p>0.05). The level of chloramphenicol in plasma was found to be higher than lymph fluid only at 2 hr (p<0.05). Concentration of trimethoprim in lymph fluids was found to be higher than plasma at 2 hr (p<0.02), but the level of lymph fluid was found to be lower than plasma at 4 hr after IM administration (p<0.002). However, levels of chloramphenicol and trimetoprim in plasma and lymph fluids were found to be similar at other sampling times. Ratios of lymph AUC(total) / AUC(total) of chloramphenicol, enrofloxacin, sulphadoxine and trimethoprim were found to be 0.97, 1.37, 0.96 and 0.86, respectively. While differences between lymph AUC(total) and plasma AUC(total) of enrofloxacin were found to be statistically significant (p<0.003), the AUC(total) of other drugs in plasma and lymph fluids were found not to be significant (p>0.05). While terminal elimination half-lives (t 1/2β) of agents in plasma were found to be 2.47, 3.35, 3.94 and 2.39, the same parameters of agents in lymph fluids were found to be 2.30, 3.73, 4.01 and 2.85, respectively. There were no significant differences between these parameters of all agents (p>0.05). The results show that when enrofloxacin, sulphadoxine and trimethoprim were used at recommended doses and intervals, these drugs penetrated peripheral tissues quickly and at sufficient concentrations, and chloramphenicol also penetrated quickly into peripheral tissue, but this dosages regimen was inadequate to supply effective concentrations in tissues.