Comparision Of Pharmacokinetics Of Florfenicol Injectable Solution, Flunixin Meglumine Injectable Solution And Florfenicol-Flunixin Meglumine Injectable Solution In Pigs

Florfenicol is a semisynthetic amide alcohols antibiotics, it has many characteristics, such as wide antimicrobial spectrum, wide distribution in the body, well absorption wether injection or oral. Florfenicol has no potential to aplastic anemia, also no teratogenic, carcinogenic and mutagenic effect, As the only dedicated to animal non-steroidal anti-inflammatory drugs(NSAIDs), Flunixin Meglumine demonstrates potent inhibition of the cyclo-oxygenase system involved in the inflammatory pathway. Florfenico-Flunixin Meglumine Injectable Solution which is made up of Florfenicol and Flunixin Meglumine is a new kind of compound preparations. Clinically used for the treatment of respiratory tract infections caused by pleural actinomycetes. By studying the pharmacokinetics parameters of Florfenicol-Flunixin Meglumine Injectable Solution, Florfenicol Injectable Solution and Flunixin Meglumine Injectable Solution in pigs, this test is used to know about Florfenicol-Flunixin Meglumine Injectable Solution pharmacokinetics characteristics as well as the comparison of corresponding active ingredient pharmacokinetics data and guide the research and invention of new drug agents and clinical administration and provide reference for the future residue eliminate research.16healthy weaning piglets were randomly divided into2groups. Among the first group, eight pigs were randomly over-cross designed, giving a20%Florfenicol-Flunixin Meglumine Injectable Solution and30%Florfenicol by intramuscular administration, respectively; Among the second group, eight pigs were randomly over-cross designed, giving respectively a20%Florfenicol-Flunixin Meglumine Injectable Solution by intravenous administration and5%Flunixin Meglumine by intramuscular administration, respectively. Blood samples were collected according to the scheduled time. The pharmacokinetics parameters were obtained by the calculating of The Winnonlin5.2pharmacokinetics analysis software on the basis of the measured blood drug concentration-time data. The florfenicol and flunixin of plasma were extracted by ethyl acetate, acetonitrile, respectively.1. Determination of florfenicol and flunuxin concentrations in plasma by HPLCThe florfenicol and flunxin of plasma were extracted by ethyl acetate or acetonitrile, respectively. The concentrations of florfenicol and flunxinin plasma were determined by reverse high performance liquid chromatography (HPLC). The conditions of HPLC for florfenicol: mobile phase was acetonitrile-0.05mol/l Potassium dihydrogen phosphate (22:78,v/v), flow rate was1.Oml/min, detection wavelength was240nm. The conditions of HPLC for flunxin:mobile phase was Methanol-0.05mol/l Potassium dihydrogen phosphate (65:35, v/v, pH=3.5), flow rate was0.8ml/min, detection wavelength was284nm.Under given chromatography conditions, the concentration of florfenicol and flunixin in pigs plasma showed a good liner coefficient relation (R2>0.9999) within the range of0.04～20mg/1and0.1～20mg/1respectively. the recoveries of florfenicol were88%-92%. The within-day CV and between-day CV were less than3%and4%; the recoveries of flunixin were84%～94%. The within-day CV and between-day CV were less than3%and4%.2. Pharmacokinetics of20%Florfenicol-Flunixin Meglumine Injectable Solution by intravenous administrationAfter intravenous administration of20%Florfenicol-Flunixin Meglumine Injectable Solution, the main pharmacokinetics parameters of Florfenicol were as followings:the mean T1/2βwas10.56h, the mean was CL(B)5.38ml/min/kg, the mean Vd was5.27hr*μg/ml, and the mean AUC was63.553(mg/l)·h; the main pharmacokinetics parameters of Flunixin Meglumine were as followings:the mean T1/2β was22.28h, the mean CL(B) was19.41ml/min/kg, the mean Vd was35.50hr*μg/ml, and the mean AUC was16.554(mg/l)·h.The results showed that the elimination of20%Florfenicol-Flunixin Meglumine Injectable Solution after intravenous administration was slow and its distribution in body was wide. comparing to the Florfenicol, the elimination of Flunixin is slower and the distribution in body was wider.3. Pharmacokinetics of30%Florfenicol Injectable Solution and5%Flunixin Meglumine Injectable Solution by intramuscular administrationAfter intramuscular administration of30%Florfenicol injectable solution, the main pharmacokinetics parameters were as followings:the mean T1/2β was25.524h, the mean Cmax was2.007mg/l, the mean Tmax was3.063h, and the mean AUC was40.638(mg/l)·h.After intramuscular administration of5%Flunix Megluminein injectable solution, the main pharm-acokinetics were as followings:the mean T1/2β was5.421h, the mean Cmax was2.926mg/l, the mean Tmax was0.729h, the mean AUC was9.265(mg/l)·h, and the absolute bioavailability was55.97%.4. Pharmacokinetics of20%Florfenicol-Flunixin Meglumine Injectable Solution by intramuscular administrationAfter intramuscular administration of20%Florfenicol-Flunixin Meglumine injectable solution, the main pharmacokinetics parameters of Florfenicol were as followings:the mean T1/2β was20.971h, the mean Cmax was4.029mg/l, the mean Tmax was1.623h, the mean AUC was56.689(mg/l)·h, and the relative bioavailability was104.62%; the main pharmacokinetics parameters of Flunixin Meglumine were as followings:the mean T1/2β was18.715h, the mean Cmax was1.863mg/l, the mean Tmax was0.441h, and the mean AUC11.334(mg/l)·h, and the relative bioavailability was122.33%.Conclusion:(1) by intramuscular administration of20%Florfenicol-Flunixin Meglumine Injectable Solution, the pharmacokinetics parameters of Florfenicol were no obvious change in the pig. Then, the elimination of Flunixin Meglumine is slow in the pig;(2) after intravenous administration, the absorption of Florfenicol is slow in the injection site, to the Flunixin Meglumine, the phenomenon only appeared in the compound preparation.