Studies On Pharmacokinetics And Tissue Distribution Of Doxycycline In Partridge Chicken

Doxycycline(DOTC)is a semisynthetic antibiotics of TCs.Compared with the natural tetracycline drugs,such as oxytetracycline and tetracycline,this drug have many advantages of stronger antibacterial activity,stronger penetrating power,wider distribution,higher bioavailability,longer elimination half-life.This drug can inhibit the activity of gram-positive bacteria and gram-negative bacteria,also inhibits the growth of rickettsia,amoeba.And the bacteriostatic effect was seven times than terramycin.This drug was usually used in animal production,playing a role to promote growth,prevent and cure diseases.Its hydrochloride was usually used in clinic,the character of its hydrochloride is crystalline powder with yellow or pale yellow,easily dissolved in water or methanol,but slightly soluble in ethanol or acetone,and almost insoluble in chloroform.Due to the wide antimicrobial spectrum,Doxycycline hydrochloride often was the first choice for the respiratory tract,urinary tract and skin soft tissue infection not only causing by abacterial infection such as rickettsia,mycoplasma,chlamydia,and relapsing fever helicoid but also listeria disease and some sensitive bacterias infection.Currently,the studies of doxycycline in pharmacokinetic mainly focused on calves,dairy cattles,goats,pigs,dogs,cats,turkeys,but the report of pharmacokinetic in partridge chickens have not seen yet.This experiment can give a reference for the clinical use of doxycycline by studying the pharmacokinetics doxycycline in partridge chicken and clarifying its changing rules.Doxycycline was administered to partridge chickens mostly by drinking water.Therefore,healthy partridge chickens were used as experimental animals to study the pharmacokinetics of doxycycline in partridge chickens after oral administration.The experiment used high performance liquid chromatography to detect the concentration of doxycycline in partridge chickens and study the pharmacokinetics in partridge chickens to understand the process of absorption,distribution,metabolism and excretion of doxycycline more clearly.But also to more scientific determination of the route of administration of doxycycline and administration time,the establishment of the determination of doxycycline pharmacokinetics and tissue distribution research methods.The purpose is to provide a reference for the safe and rational drug use in clinical practice.The medicine was given orally gavage to partridge chickens and collect venous blood under the wings at different time points after administration.And plasma samples collected for testing by HPLC with the purpose to research the pharmacokinetic characteristics of doxycycline in partridge chicken.The medicine was given orally gavage to partridge chickens and killed the partridge chicken collect tissues at different time points after administration.And tissue supernatan collected for testing by HPLC with the purpose to research the pharmacokinetic characteristics of doxycycline in partridge chicken.The plasma samples were treated with acetonitrile liquid-liquid extraction,and choosed oxytetracycline as the internal standard.HPLC is Shimadzu LC-20A,chromatographic column is shimadzu WondaSil-Ci8-WR(150x4.6 mm,5?m),detective wavelength is 350 nm,mobile phase is N,N-DMF-0.05 mol/L ammonium oxalate solution(40:60,V/V,ammonia water adjusted pH 7.5 ± 0.2),the flow rate is 0.8 mL/min,column temperature is 30 ?,the injection volume is detected with 20?L of chromatographic conditions.By the study of pharmacokinetic found that the pharmacokinetic parameters generation of partridge chicken with doxycycline oral given 20 mg/kg was showed as follow.The Cmax of peak plasma concentration was(2.88 ± 2.39)?g/mL,Tmax to peak was(0.78±0.35)h,elimination half-life ti a was(6.36 ± 2.27)h,the elimination rate constant was(0.12 ± 0.04)h-1,AUC0-t was(19.05 ± 12.77)?g·h·mL-1,AUC0?? was(19.27 ± 12.95)?g·h·mL-1,the mean residence time was(7.57 ± 1.72)h,clearance CLtot was(36.18 ± 41.93)mL·min-1,the apparent distribution volume Vd was(23.84 ±33.23)L·kg-1.The concentration of doxycycline is widely distributed in partridge chickens.The content of doxycycline in the liver,kidney and duodenum is obviously higher than that of other tissues.It can also penetrate the blood-brain barrier and blood-testis barrier.Therefore,doxycycline can be used in the veterinary clinic for systemic infection of partridge chickens.