Pharmacokinetics Of Ketoprofen In Cows

Ketoprofen(KP),also called profenid,2-(phenyl 3-benzoyl)propionic acid is a Non-steroidal anti-inflammatory drug belonging to the arylpropionic acid group.The primary mechanism of action for ketoprofen is considered to be inhibition of the cyclooxygenase pathway of arachidonic acid metabolish,leading to decreased production of inflammatory mediators,such as prostaglandins and thromboxanes.This mechanism of action results in its anti-inflammatory,anti-pyretic and analgesic activity.Oral ketoprofen can cause serious gastrointestinal(GI)side effects,related to its pharmacological mechanism and function,thus it is limitedly to in clinical medicine.Intravenous ketoprofen is currently available in human medicine,which decreases ketoprofen-induced intestinal adverse events as intravenous administration could avoid direct contact with GI.Ketoprofen has been increasingly applied in veterinary medicine,and widely used in pigs,horses,cattle,goats,ect.in foreign countries.In cows,ketoprofen is used to treat diseases caused fever,pain and inflammation such as mastitis,breast edema,arthritis and musculoskeletal trauma.In the European Union,maximum residue limit for ketoprofen in edible tissues of different food-producing animals has not be established.According to previous studies,ketoprofen has shown superior pharmacological function to some other non-steroidal anti-inflammatory drugs,thus the development of ketoprofen injection for animals has a broad market prospect and also prompts farming industry in China.This experiment were investigated the pharmacokinetics and bioavailability of intramuscular ketoprofen injection in healthy Holstein cows.Six healthy adult Holstein cows were divided randomly into two groups.The experiment was carried out according to a randomized cross-over design and pharmacokinetics of ketoprofen were investigated following single intravenous(3mg/kg)and intramuscular(3mg/kg)adminstration.Collecting the blood blank sample before administration of ketoprofen,the blood sample were collected at different time points(5,10,15,20,30,40,50 min and 1,1.5,2,3,4,6,8,10,12,14,16,24,30,36,48h).The ketoprofen concentrations in plasma were determined by high performance liquid chromatography with tandem quadrupole mass spectrometry(HPLC-MS/MS).The concentration-time data of ketoprofen in plasma were analyzed with Win Nonlin 5.2.1 computer program.The concentration-time data of ketoprofen in plasma after single intravenous dosing in healthy Holstein Cows were fitted to a two-compartment open model.The main pharmacokinetic parameters were as follows(mean?S.D):T1/2?=0.420?0.06 h,T1/2?=2.460?0.34 h,V(C)=0.100?0.01L/kg,V(d)=0.503?0.09L/kg,C lB=0.142?0.02(L/kg)·h,AUC=21.469?3.12(?g/m L)·h.The concentration-time data of ketoprofen in plasma after single intramuscular dosing in healthy Holstein Cows were fitted to a two-compartment open model with first-order absorption.The main pharmacokinetic parameters were as follows(mean?S.D): T1/2Ka=0.311?0.22 h;T1/2?=1.630?0.14 h,T1/2? =5.538?0.59 h,ClB=0.142?0.02(L/kg)·h,Tmax=0.987?0.35 h,Cmax=4.968?0.73?g/m L,AUC=19.878?3.56(?g/m L)·h,bioavailability F 92.48%?7.76%.The results of the studies showed that the pharmacokinetic characteristics of ketoprofen in healthy Holstein Cows were as following: intravenous dosing with rapid anddrug main distributed in the centralcompartment,quick elimination,intramuscular dosing rapid absorption and short time to peak,high peak concentration and high bioavailability.