Pharmacokinetics Of Tilmicosin In Healthy Chickens And Experimental Infected Models With Mycoplasma Gallisepticumin

Tilmicosin is a macrolide antibiotic formed from a chemical mod ification of tylosin.It is one of the most ideal medicines in the clinical treatment for the Mycoplasma gallisepticum infection,with its great antimicrobial activity against Mycoplasma gallisepticum and good penetration in lung.The aim of the present research was to study the pharmacokinetic of tilmicosin in healthy chickens and the Mycoplasma gallisepticum experimental infected chickens.The infected chickens were randomly divided into three groups and they were performed with tilmicosin by oral administration at a single dose of 4 mg/kg b.w.,7.5mg/kg b.w.,10 mg/kg b.w.,respectively.While the healthy chickens were orally administered with tilmicosin at a single dose of 7.5 mg/kg b.w..Samples of plasma and lung were collected from each bird at the time of slaughter.The concentrations of tilmicosin in samples were determined by high performance liquid chromatograpy tandem mass spectrometry?HPLC-MS/MS?.Pharmacokinetic analysis was performed using WinNonLin5.2.1 programe.The Mycoplasma gallisepticum infected models were developed in 2-day age broiler chickens.They were induced with 0.2 mL rejuvenated Mycoplasma gallisepticum S6 strain bacteria culture at approximately 5×10⁹ colony-forming units?CFU?/mL,via trachea way,twice a day for three days.The model was evaluated by clinical symptoms,pathologic anatomy,pothogen indentification and Mycoplasma gallisepticum test kit detection.The results displayed that the Mycoplasma gallisepticum experimental infected model in chicken was successfully established.After orally administrated at a single dose of 7.5 mg/kg b.w.in the healthy chickens,the concentration-time data in plasma conformed to the non-compartment model.The main pharmacokinetic parameters in plasma of healthy group were as followed:t_1/2kel was 22.67 h,T_max was 1 h,C_max was 0.09?g/mL,AUC_?0-24h?was 0.82?g·h/mL and MRT was 30.87 h.By contrast,the concentration-time data in lung of healthy chickens conformed to the one-compartment with first-order absorption model.The main pharmacokinetic parameters in lung were as followed:t_1/2kel was 32.45 h,t_1/2ka was 1.83 h,T_max was 8.05 h,C_max was1.02?g/mL,AUC_?0-24h?was 20.71?g·h/g.In addition,after orally administrated of tilmicosin at a single dose of 4,7.5,10 mg/kg b.w.in the diseased chickens,the resulted showed that,whether in plasma or in lung,the concentration-time data conformed to the same model as the healthy group.It is obvious that the values of the C_max and the AUC_?0-24h?were in proportion to the dose both in plasma and in lung.Moreover,the pharmacokinetic parameters of plasma in infected groups were as followed:t_1/2kel was in the range of?20.31²3.98?h,C_max were 0.05,0.09 and 0.12?g/mL,respectively.AUC_?0-24h?were 0.46,0.78 and 1.02?g·h/mL,respectively.Furthermore,the pharmacokinetic parameters of lung in infected groups were as followed:t_1/2ka was in the range of?4.44⁵.86?h,t_1/2kel was in the range of?41.56⁴4.88?h,C_max were 0.44,0.99 and 1.70?g/g,respectvely.AUC_?0-24h?was9.42,20.25 and 37.72?g·h/g,respectvely.The pharmacokinetic parametres in plasma and in lung had disrepancy,which showed that the rate of the absorption and elimination in the lung were both slower than in plasma,but the distribution of drug was more extensive and the maitentance time was longer than that in plasma.On the other hand,comparing with the pharmacokinetic parametres between healthy group and diseased groups,there was no significant difference in plasma of these groups,while the rate of the absorption and elimination in infected model were remarkably increased than that in the healthy birds.In general,these results indicated that,tilmicosin was rapidly absorbed and distributed after oral administration,but was eliminated slowly in the healthy chickens.In addition,tilmicosin had strong penetrating power in lung.Furthermore,although there was no cospicuous difference in plasma of chicken with Mycoplasma gallisepticum in infection,the rate of metabilism in the lung of the infected chickens were markedly decreased,with slowed absorbability,slowed elimination and prolonged maitentance time.