Pharmacokinetic Of Acetylkitasamycin In Swine And Broilers

Compared with kitasamycin,acetylkitasamycin has the characteristics of good palatability,high stability and safety.Therefore,it is worthy to promote the use of acetylkitasamycin in breeding industry.The promotion of new veterinary drugs must be listed through the pharmacokinetic study of preclinical trials.So,this topic uses the intravenous injection and 3 doses of oral administration to do the pharmacokinetic in swine and broiler.The drug concentrations in plasma of swine and broilers were measured by Winnonlin pharmacokinetics software.Based on the calculated values under different administration ways of the pharmacokinetics of oral drug utilization to the absolute bioavaibility and the pharmacokinetic characteristics.1 Establishment of quantitative confirmatory methodDue to the complexity of acetylkitasamycin components,ultimately,we choose 12 components of acetylkitasamycin A6A7,A4A5,A1A3,A,3,A5’as well as the corresponding components of kitasamycinA7,A6,A5,A4,A1,A3,A13 as quantitative of pharmacokinetic study after analysis of the components about acetylkitasamycin.The plasma of swine and broiler was extracted with acetonitrile and the protein was precipitated,then extracted by ethyl acetate for two times,concentrated by nitrogen,dissolved with complexed solution of water:acetonitrile =60:40(V:V),n-hexane was added to remove the fat and discard the n-hexane layer for LC-MS/MS detection.The LOD and LOQ of kitasamycinA3,A13 and acetylkitasamycin A1A3,A13 in swine plasma were 1 μg/L and 3 μg/L respectively,the LOD and LOQ of others 8 components were 2μg/L and 5 μg/L respectively;The LOD and LOQ of kitasamycin A3,A3 and acetylkitasamycin A1A3 in broiler plasma were 1 pg/L and 3 μg/L respectively,the LOD and LOQ of others 9 components were 2 μg/L and 5 μg/L respectively.The average recovery rate was 85.3%～103.5%,the coefficient of variation was less than 14.3%.2 The pharmacokinetic of acetylkitasamycin in swine24 healthy landrace swine were selected,which were grouped into 50,100 and 200 mg/kg b.w.single oral dose and 20 mg/kg b.w.intravenous of acetylkitasamycin,about 4-5mL blood sample was collected from jugular vein in the design of the time after administration;Each single component was quantitatived by LC-MS method,the concentration-time curve of the different ways of administration and different doses were drawn,the pharmacokinetic parameters were calculated by non compartmental method by Winnonlin software.10 components of intravenous group can be detected except kitasamycinA7 and A6,the concentration of acetylkitasamycin components was much higher than kitasamycin components at same timepoints,the highest concentration of kitasamycin components is kitasamycinA4.The half lives of all components were within 0.1～0.4 h,the apparent distribution volumes of every components were large.The results showed that after intravenous injection of acetylkitasamycin,it’s distributing and eliminating were fast and it was widely distributed in the tissues of swine.The absorption and elimination of acetylkitasamycin components were fast,and the concentration were low.Dose of 50 mg/kg b.w.oral acetylkitasamycin can be observed the other four acetylkitasamycin components except A,3 and kitasamycinA4,A1 and A3 can also be observed.It can be observed 5 acetylkitasamycin components and 5 kitasamycin components except kitasamycinA7 and A6 at the oral dose of 100 and 200 mg/kg b.w.The concentration of acetylkitasamycin components were higher than kitasamycincomponents at 3 oral doses,it showed that the effection of acetylkitasamycin by oral administration in swine mainly based on acetylkitasamycin.The half lives of acetylkitasamycin components were short,showed the elimination of acetylkitasamycin components were fast,and the Vd values of every components were large,showed that the distribution in the body tissue was extensive.Compared with the pharmacokinetic parameters about 3 doses of oral administration with acetylkitasamycin A4A5 and A5’,changes of elimination,half lives,MRT value and Cl values were not obvious with the increasing of doses and the value of Cmax and AUC had a linear relationship with the dose,showed that in 50～200 mg/kg b.w.dose may follow a linear kinetic characteristic.According to the formula,the oral bioavaibility of acetylkitasamycin in swine was 9.6%～14.96%.2 The pharmacokinetic study of acetylkitasamycin in broiler48 healthy white Feathered broiler were selected,which were grouped into 100,200 and 400 mg/kg b.w.single oral dose and 50 mg/kg b.w.intravenous of acetylkitasamycin,about 1～2mL blood sample was collected from Inferior vena cava in the design of the time after administration;Each single component was quantitatived by LC-MS method,the concentration-time curve of the different ways of administration and different doses were drawn,the pharmacokinetic parameters were calculated by non compartmental method by Winnonlin software.5 components of acetylkitasamycin can be detected of the intravenous group,the half lives of all components were within 0.022～0.15 h,the apparent distribution volumes of every components were large.The results showed that after intravenous injection of acetylkitasamycin,it’s distributing and eliminating were fast and it was widely distributed in the tissues of broiler.The absorption and elimination of acetylkitasamycin components were fast,and the concentration were low at the dose of 100、200、400 mg/kg b.w.Dose of 100 mg/kg b.w.all acetylkitasamycin components can be observed,but kitasamycin components could not be observed.It can be observed 5 acetylkitasamycin components and kitasamycinA4 at the oral dose of 200 and 400 mg/kg b.w.The concentration of acetylkitasamycin components were higher than kitasamycinA4.The half lives of acetylkitasamycin components were short,showed the elimination of acetylkitasamycin components were fast,and the Vd values of every components were large,showed that the distribution in the body tissue was extensive.Compared with the pharmacokinetic parameters about 3 doses of oral administration with 5 acetylkitasamycincomponents,changes of elimination,half lives,MRT value and Cl values were not obvious with the increasing of doses and the value of Cmax and AUC had a linear relationship with the dose,showed that in 100～400 mg/kg b.w.dose follow a linear kinetic characteristic.According to the formula,the oral bioavaibility of acetylkitasamycin in swine was 13.85%～15.7%.