Pharmacokinetics And Bioavailability Of Amoxicillin Dry Suspension In Swine After Oral Administration

Amoxicillin(AMO)is a broad-spectrum acid-resistant penicillin antibiotics that has been widely used in veterinary clinic for the treatment of infections caused by gram-positive and gram-negative bacteria.The preparations are approved for use in cows,pigs,poultry,horses,dogs and cats.AMO is commonly used as an antibiotics in animal production and veterinary medicine and has good absorbability and easy penetration into tissues.Aqueous and oily formulations for parenteral administration in pigs(intravenous,subcutaneous and intramuscular)have gained global recognition.There have been a series of reports on the pharmacokinetics of amoxicillin in pigs.However,pharmacokinetic studies of amoxicillin dry suspension have not been reported yet in pigs.Therefore,the present study was conducted on pharmacokinetic characteristics and bioavailability in pigs after the oral administration of amoxicillin dry suspension,which provided a rational basis for the clinical use of amoxicillin dry suspension in pigs.Eight healthy crossbred swine were randomly divided into two groups.The experiment was carried out according to a randomized crossover design and Pharmacokinetics of oral amoxicillin dry suspension(10 mg/kg)and intravenous amoxicillin sodium injection(10 mg/kg).One week later,the pigs of the two groups were tested for the exchange route of administration.Collecting the blood blank sample before administration of amoxicillin,the blood sample were collected at different time(5,10,15,30,45 min and 1,1.5,2,3,4,6,8,10,12,14,24 h)after administration.The amoxicillin concentration in plasma was determined by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).After the plasma sample was added to the internal standard,the protein was removed by acetonitrile,diluted with ultrapure water,and then tested on a constant volume.The concentration time data of amoxicillin in plasma were analyzed with WinNonlin 5.2.1 pharmacokinetic program.After oral administration of amoxicillin dry suspension(10 mg/kg),the plasma drug concentration gradually increased,absorbed rapidly and peak time was short.After 24 h,the amoxicillin concentrations in all plasma samples were below 0.1 μg/mL.The specific pharmacokinetic parameters were as follows:Tmax(1.38±0.35)h,t1/2(1.52±0.46)h,Cmax(4.69±0.91)μ/mL,AUC(0-t)(13.27±3.63)(μ/mL)h,AUC(0-∞)(13.44±3.56)(μg/mL)h,MRT(2.92 ± 0.63)h.The bioavailability of the amoxicillin dry suspension was(90.55±16.14)%,indicating that the amoxicillin dry suspension was almost completely absorbed orally.After intravenous injection of amoxicillin sodium(10 mg/kg),the drug was rapid distribution and eliminated quickly.The specific pharmacokinetic parameters were as follows:t1/2(2.19±0.62)h,Cmax(21.68±4.19)μ/mL,AUC(0-t)(14.51 ±2.02)(μg/mL)h,AUC(0-∞)(14.67±2.04)(μg/mL)h,Vd(2.19±0.74)L/kg,Vss(0.99±0.31)L/kg,CLB(0.69±0.09)L/h/kg,MRT(1.27±0.16)h.The experimental results show that the pharmacokinetic characteristics of oral amoxicillin suspension in swine was rapid distribution,short peak time,high peak concentration,rapid elimination,and highbioavailability.The pharmacokinetic characteristics of amoxicillin after iv administration in healthy swine was rapid distribution and rapid elimination.