Comparative Study Of Pharmacokinetics Of Long-Acting Enrofloxacin Injection In Pigs

Enrofloxacin is a fluoroquinolone,a class of broad-spectrum antimicrobial,scientifically recommended in the therapy in livestock including pigs,calves,bovines and for diseases of the urinary,urogenital,and respiratory tracts and for skin diseases.Fluoroquinolones have significant levels of distribution and a low degree of plasma protein binding,and they are also widely dispersed across the body.They are absorbed with increased bioavailability following oral and parental administrations from the gastrointestinal tract and operate at very low levels.Because of the fast effects and large range of antibacterial activities,fluoroquinolone is used extensively in veterinary practice.Enrofloxacin is a significant component of the fluoroquinolone family and has an outstanding activity to suppress DNA production against mycoplasma,Gram-positive and Gram-negative pathogens.ENR blocks the actions of the bacterial DNA-gyrase and topoisomerase IV enzymes directly.Its killing rate is concentration-based,and it has a post-antibiotic impact.Long-term usage of fluoroquinolones,on the other side,will result in a rise in antimicrobial resistance in animals as well as medication residues in animal muscle and tissue,presenting a potential hazard to human health across the food chain.Pharmacokinetics and pharmacodynamics(PK/PD)simulation could aid with dose optimization and resistance prevention.PK/PD modeling is an important method for determining the clinically relevant interaction between time and impact.Because of the strong alkalinity of the traditional enrofloxacin injection,its clinical application is still limited,and it cannot be compatible with other drugs that can play a synergistic bactericidal effect.Existing short-acting preparation of enrofloxacin drugs shows a short half-life,low efficacy,inefficient therapeutic effect,needed for repeated drug use in a short time,resulting in a large amount of drug use with high costs.Frequently uses of drugs may cause multi-drug residues.Very few single-dose long-acting formulations are available in the market.In most of the case,the treatment is less effective and requires to use for 3 to 5 consecutive days lead to a large number of residual drugs in animals.In this research,a comparative study on pharmacokinetics of four long-acting enrofloxacin injectable formulations was investigated in 36 healthy pigs after intramuscular injection according to the recommended single dose@2.5 mg/kg body weight.The aim of this research was to study enrofloxacin's pharmacokinetic properties in plasma after intramuscular(IM)dosing.The drug concentrations in the plasma were computed using high-performance liquid chromatography(HPLC)with fluorescence detection.Win Non Lin5.2.1 software was used to analyze the experimental data and compared it under one-way ANOVA using SPSS software with a 95%confidence interval(CI).The main pharmacokinetic parameters,the maximum plasma concentrations(C_max),the time to maximum concentration(T_max),area under the time curve concentration(AUC_all)and Terminal half-life(T_1/2)were 733.84±129.87,917.00±240.13,694.84±163.49,621.98±227.25 ng/m L,2.19±0.0.66,1.50±0.37,2.89±0.24,0.34±0.13hours,7754.43±2887.16,8084.11±1543.98,7369.42±2334.99,4194.10±1186.62 ng h/m L,10.48±2.72,10.37±2.38,10.20±2.81,and 10.61±0.86 hours for 10%enrofloxacin(Alkali),20%enrofloxacin(Acidic),Yangkang and control drug Nuokang^R respectively.There were significant differences among C_max,T_max,and AUC_all of three formulations compare with those of the reference formulation.No significant differences were observed among the T_1/2 for tested formulations compare with the reference formulation.The pharmacokinetic parameters showed that the tested formulations were somewhat better compared to the reference one,but the dose was not sufficient to afford the required AUIC and C_max/MIC values for agents acting primarily by concentration-dependent mechanisms.