Pharmacokinetics And Bioavailiability Of Compound Tilmicosin Soluble Powder In Healthy Broilers

The purpose of the present study was to develop the high performance liquid chromatography?HPLC?methods for the determination of timicosin and sulfamethazine concentration in chicken plasma and determine the main pharmacokinetic parameters of tilmicosin and Sulfamethazine in healthy broilers after oral administration of compound tilmicosin soluble powder.The eluates were determined by HPLC.Limits of detection?LOD?were 0.02 mg/m L for both timicosin and sulfamethazine,and Limits of quantification?LQD?were 0.05 mg/m L for both timicosin and sulfamethazine in chicken plasma.Recoveries of timicosin and sulfamethazine were 82.38%¹08.75% and 80.34%⁹3.40% for chicken plasma fortified at 0.05,0.5,5 mg/m L.Coefficients of variation were in the range of 2.25%⁴.33% and 2.29%⁴.32%.Thirty-six clinically healthy Sanhuang Broilers were randomly divided into three groups by sex and bodyweight,every group has twelve and the average weight was respectively 1.68±0.19 kg,2.02±0.08 kg,2.07±0.19 kg,and were respectively administrated of compound tilmicosin soluble powder as a single oral,of tilmicosin injection as a single intramuscular injection,of salfadimidine injection as a single intravenous injection.Tilmicosin and salfadimidine concentrations were assayed by HPLC.The main pharmacokinetic parameters were determined by means of the Win Nonlin6.1 corresponded to the noncompartmental pharmacokinetic model.Salfadimidine plasma concentration reached its peak level(C_max)10.03 mg/m L at 2.25 h after oral administration.The average elimination half-life?t1/2?was 1.38 h,the area under concentration time curve?AUC?was 37.17 ?g×h/m L,the mean retention time?MRT?was 3.95 h,the apparent volume of distribution?Vz?was 1.09 L/kg.Nine hours after oral administration,Tilmicosin concentrations reached its peak level(C_max)1.43mg/m L;The average elimination half-life?t1/2?was 12.24 h,the area under concentration time curve?AUC?was 9.49 ?g×h/m L,the mean retention time?MRT?was 11.75 h,the apparent volume of distribution?Vz?was 35.00 L/kg.Tilmicosin presented a rapid absorption afer intramuscular adminiatration?20mg/kg b.w.?,the tilmicosin plasma concentration reached its peak level(C_max)2.33 mg/m L at half an hour after administration,The average elimination half-life?t1/2?was 8.99 h;the area under concentration time curve?AUC?was 12.40 ?g×h/m L,the mean retention time?MRT?was 10.69 h,the apparent volume of distribution?Vz?was 20.56 mg/m L.Salfadimidine plasma concentration also presented a rapid absorption afer intravenous adminiatration?20mg/kg b.w?,the salfadimidine plasma concentration reached its peak level(C_max)22.99 mg/m L at 0.083 h after administration.The average elimination half-life?t1/2?was 1.26 h;the area under concentration time curve?AUC?was 61.31 ?g×h/m L,the mean retention time?MRT?was 2.50 h,the apparent volume of distribution?Vz?was 0.60 L/kg.The bioavailability of compound tilmicosin soluble powder by intramuscular injection in chickens were respectively 75.98% for tilmicosin and 60.63% for salfadimidine;Compared with the single drug administration,the compound tilmicosin soluble powder was absorbed slowly afer oral administraton,the Tmax was significantly dealayed,the mean retention time?MRT?was prolonged,the effective blood drug concentration maintenance time was prolonged,the result showed the combinations were advantageous to the antibacterial effect.