| Gamithromycin is a semi-synthetic macrolide,belongs to the animal-special antimicrobial drug.The broad spectrum antimicrobial activity of gamithromycin includes Mannheimia haemolytica,Pasteurella multocida and Histophilus somni,the bacterial pathogens most commonly associated with Bovine Respiratory Disease(BRD).This experiment aimed to establish simple efficient,and sensitive UPLC-MS/MS method for determination of Gamithromycin in plasma and the method was applied to the pharmacokinetics study.And evaluated the safety of Gamithromycin injection in swines.The experiment are as following:1 Establishment of UPLC-MS/MS detection Gamithromycin in swine plasmaThe plasma sample is extracted with acetonitrile,quantified by internal standard,detected by UPLC/MS-MS.The results showed that the drug in plasma showed good linear relationship at the range of 1～500 μg/L and the correlation coefficients were greater than 0.99(R2>0.99),the mean average recoveries of spiked samples ranged from 86.95%to 119.00%with relative standard deviation(RSD)less than 7.85%.The limits of detection(LOD)and quantification(LOQ)in plasma were 0.5 and 1 μg/L respectively.2 The pharmacokinetics study of Gamithromycin in swinetwenty-four healthy swines(15 ± 1 kg)were randomly divided into three groups,swines were treated with either a single intravenous dose of 6 mg/kg b.w gamithromycin or with a single intramuscular.Each group comprised 8 animals.The third group were treated with a single intramuscula dose of 6 mg/kg bw Zactran(?)gamithromycin(Merial,Duluth,GA,USA).After treatment,blood was collected from the treated swine at approximately at 0,083,0.13,0.17,0.25,0.50,0.75,1,2,4,6,8,12,24,36,48,72,96,120,144 h,and 168 h post administration.Blood sample were collected and analyzed according to the predetermined time and using the pharmacokinetic software Winnonlin with noncompartmental model.The first group of parameters were as followed:the mean area under the curve extrapolated to infinity(AUC0→t)was 6578.4±2049.4 h-ng·mL-1,and the mean terminal plasma half-life(T1/2λz)was 31.6±5.8 h.The volume of distribution(Vd)and observed clearance(Cl)were 41221.2± 10335.5 mL·kg-1 and 917.4 ± 216.2 mL·kg·h-1,respectively.The second group of parameters were as followed:The mean maximum plasma time and concentrations were 0.119±0.031 h and 1748.7±554.2 ng·mL-1,T1/2λz was 20.4±5.4 h,AUC0→t was 5854.7±2169.7 h·ng·mL-1,Vd was 30521.6±8531.6 mL-kg-1,Cl was 1078.5±295.9 mL·kg·h-1.The third group of parameters were as followed:Tmax and Cmax were 0.325±0.347 h and 1064.5± 160.8 ng·mL-1,respectively.AUC0→t was 5219.6 ±1858.7 h·ng·mL-1,Vd was 44475.8 ± 17829.9 mL·kg-1,Cl was 1365.0 ± 969.2 mL·kg·h-1.The absolute bioavailability and relative bioavailability were 89.00%and 112.17%,respectively.3 The safety study of Gamithromycin in swineTwenty-four adult healthy swines weighted 15～25 kg were randomly devided into 4 groups(n=6,each group).They are a control group and three medicated groups by intramuscular administration for three days with the doses 0 mg/kg(control),6 mg/kg(the recommended dose),18 mg/kg(3 times the recommended dose),30 mg/kg(5 times the recommended dose).The adverse drug reactions were not observed during administration periods,The results shows that recommend dose of gamithromycin injection had no significant effect on swine blood physiological and biochemical parameter,average daily gain and average daily feed intake were not significantly decreased.And,Contral group and 5 times the recommended dose operation group was no changes in heart,liver,spleen,lung,kidney and brain.This conclusion suggests that intramuscular taking gamtthromycin in the dose of 6 mg/kg was safe to use as a respiratory disease drug. |
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