Bazı antimikrobiyel ilaçların plazma ve lenf sıvısındaki farmakokinetik profillerinin karşılaştırılması

Abstract

7. SUMMARY Comparasion of Pharmacokinetic Profiles of Some Antimicrobial Agents in Plasma and Lymph Fluids In this study, some pharmacokinetic parameters and concentrations of four antimicrobial agents in plasma and lymph fluids were compared for determine penetration into peripheral tissues. Eighteen healthy, adult sheep (Turk Merino x Hampshire cross, 18-24 month, weighing 32-37 kg) were used, as materials. For collecting of lymph samples, the efferent vessel of Nl. 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., Sulphadoxme-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 higher than plasma (p< 0.01), but concentrations of sulphadoxine in plasma and lymph fluids at all sampling times were not found statistically differences (p> 0.05). Level of chloramphenicol in plasma was found higher than lymph fluid only at 2 hr (p< 0.05). Concentration of trimethoprim in lymph fluids was found higher than plasma at 2 hr (p< 0.02), but its level of lymph fluid was found lower compare to plasma at 4 hr after İM administration (p< 0.002). However, levels of chloramphenicol and trimetoprim in plasma and lymph fluids were found similar at other sampling times. Ratios of lymph AUC(totai) / plasma AUC(totai) of chloramphenicol, enrofloxacin, sulphadoxine and trimethoprim were found 0.97, 1.37, 0.96 and 0.86, respectively. While differences between lymph AUQtaai) and plasma AUQwan of 46eiirofloxacin were found statiscally significant (p< 0.003), AUC(totai) of other drugs in plasma and lymph fluids were found no significantly (p> 0.05). While terminal elimination half-life (t 1/2 P) of agents in plasma were found 2.47, 3.35, 3.94 and 2.39, same parameters of agents in lymph fluids were found 2.30, 3.73, 4.01 and 2.85, respectively. It was not significantly differences between this parameters of all agents (p> 0.05). The result show that when enrofloxacin, sulphadoxine and trimethoprim were used at recommended doses and intervals, these drugs penetrated quickly and enough concentrations into peripheral tissues, and also chloramphenicol penetrated quickly into peripheral tissue but this dosages regimen was inadequate to supply effective concentrations in tissues. 47

7. SUMMARY Comparasion of Pharmacokinetic Profiles of Some Antimicrobial Agents in Plasma and Lymph Fluids In this study, some pharmacokinetic parameters and concentrations of four antimicrobial agents in plasma and lymph fluids were compared for determine penetration into peripheral tissues. Eighteen healthy, adult sheep (Turk Merino x Hampshire cross, 18-24 month, weighing 32-37 kg) were used, as materials. For collecting of lymph samples, the efferent vessel of Nl. 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., Sulphadoxme-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 higher than plasma (p< 0.01), but concentrations of sulphadoxine in plasma and lymph fluids at all sampling times were not found statistically differences (p> 0.05). Level of chloramphenicol in plasma was found higher than lymph fluid only at 2 hr (p< 0.05). Concentration of trimethoprim in lymph fluids was found higher than plasma at 2 hr (p< 0.02), but its level of lymph fluid was found lower compare to plasma at 4 hr after İM administration (p< 0.002). However, levels of chloramphenicol and trimetoprim in plasma and lymph fluids were found similar at other sampling times. Ratios of lymph AUC(totai) / plasma AUC(totai) of chloramphenicol, enrofloxacin, sulphadoxine and trimethoprim were found 0.97, 1.37, 0.96 and 0.86, respectively. While differences between lymph AUQtaai) and plasma AUQwan of 46eiirofloxacin were found statiscally significant (p< 0.003), AUC(totai) of other drugs in plasma and lymph fluids were found no significantly (p> 0.05). While terminal elimination half-life (t 1/2 P) of agents in plasma were found 2.47, 3.35, 3.94 and 2.39, same parameters of agents in lymph fluids were found 2.30, 3.73, 4.01 and 2.85, respectively. It was not significantly differences between this parameters of all agents (p> 0.05). The result show that when enrofloxacin, sulphadoxine and trimethoprim were used at recommended doses and intervals, these drugs penetrated quickly and enough concentrations into peripheral tissues, and also chloramphenicol penetrated quickly into peripheral tissue but this dosages regimen was inadequate to supply effective concentrations in tissues. 47