Comparative Pharmacokinetics Of Two Gamithromycin Injection In Cattles

Gamithromycin is a new kind of semi-synthetic macrolide veterinary medicinal product for veterinary use only.It had been proved to be used for the treatment of BRD caused by Mannheimia Haemolytica,Pasteurella Multocida,Histophilus Somni,and Mycoplasma Bovis by EMEA（European Medicines Agency）,HPFB（Health Products and Branch）and FDA（Food anddrug Administration）.Gamithromycin presents excellent pharmacokinetics characteristics and high bioavailability in cattles.High concentration of gamithromycin in lung tissues resulted from quick absorption and distribution by one subcutaneous injection dose of 6mg/kg.bw.Besides,residues in cattle tissues is low that is a good characteristic for food safety.The objective of this study was to evaluate a homebred gamithromycin injection by comparing the pharmacokinetic parameters between the homebred gamithromycin injection and ZACTRAN.It represents a valuable singnificance of the application of the homebred gamithromycin injection.We set a parallel experiment that twenty-one 4 months old cattles weighting115.63±21.93kg which were rando mly divided into three groups.O ne group received a subcutaneous injection of the homebred gamithromycin injection,while the other two groups received injection of ZACTRAN by subcutaneous and intravenous respectively.Each group received a injection dose of 6 mg/kg.bw.Blood samples were collected at the time of 5min,10min,15min,30min,1h,2h,4h,8h,10h,12h,1and13d after administration.And the concentration of gamithromycin in plasma was detected by HPLC-MS/MS.The concentration-time data was analyzed by WinNonLin 5.2.1.The pharmacokinetic parameters were as follows.In the introuvaneous injection group,the elimination half life(t_1/2)was 36.60±2.33h,the area under the curve（AUC）was4754.60±363.49 ng·h·L^-1,the apparent volunme of distribution was（Vd）65.31±6.72 L·kg^-1and the clearance（CL）was 1242.90±97.59 mL·h^-1·kg^-1.In the subcotaneous injection group of ZACTRAN,the elimination half life(t_1/2)was 48.85±3.83 h,the area under the curve（AUC）was 4736.92±343.53 ng·h·L^-1,the C_max and T_max were 392.7±52.24ng/mLand0.50±0.00 h.In the subcotaneous group of the homebred gamithromycin injection,the elimination half life(t_1/2)was 49.16±1.83 h,the area under the curve（AUC）was 4918.32±605.10 ng·h·L^-1,the C max and Tmax were 389.57±33.10ng/mLand0.51±0.29 h.The absolute bioavailability of the homebred gamithromycin injection and ZACTRAN were 105.2%and 99.6%respectively.And the relative bioavailability of the homebred gamithromycin injection to ZAC TRAN was 103.8%.Resluts showed that both the homebred gamithromycin injection and ZACTRAN present a quick absorption,extensive distribution,slow elinimation and high bioavailability in cattles.There is no significant difference between the homebred gamithromycin injectio n and ZACTRAN in pharmacokinetic parameters.