| Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to give drug dose that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis, therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimize the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and minimize the emergence of resistance. The aim of this study is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy and disease model.For Pharmacokinetic study an HPLC assay was developed. A sensitive high performance liquid chromatography(HPLC) is a renowned method for the determination of Cefquinome in blood plasma. The plasma samples of Cefquinome were extracted with HLB and separated by HPLC on a reversed phase C-18 column with mobile phase of 0.1% formic acid solution-acetonitrile(90:10, v/v). The calibration curves were linear ranged from 0.01-5μ g/ml. The limit of detection(LOD) and limit of quantification(LOQ) were 0.01 and 0.04 μ g/ml. The recovery of Cefquinome from plasma was 73.4 %, 78.33 %, and 77 % for low, medium and high concentration samples. The intra and inter day relative standard deviation were less than 15 %. The Cefquinome were found to be stable for more than 3 months at-70 0C and more than 24 hours at 40 C. The present method has been successfully applied for the pharmacokinetics study in cattle. After intramuscular administration, the mean peak serum Concentrations(Cmax) was found 2.95 μg/m L and achieved after(Tmax) 1.50 h. The elimination half-life(tl/2(el)) was 2.03±0.06 hrs. The Mean Residence Time(MRT) was 2.58±0.05 hrs and area under curve from zero time to infinity(AUC0-∞) was 9.67±0.72 μg/m L/h. The newly proposed method was shown to be simple, rapid, economical and sensitive compared to the previously reported method, and thereafter applicable for the pharmacokinetics study in animals.After assay developed for Cefquinome determination, the ex vivo activity of Cefquinome against Staphylococcus aureus strains by using bovine serum from intravenous treated cattle. Cefquinome kinetics were measured by liquid chromatography and UV detection. Different pharmacodynamics experiment were performed, such as MIC, MBC, In vitro post antibiotic effects(PAEs) and mutant prevention concentration were determined with S. aureus strain ATCC 12598. Cefquinome exhibited time-dependent killing and produced in vitro PAEs increasing with concentration and time of exposure. The 110 Staphylococcus aureus were selected and subjected to MIC determination by agar dilution method. The MIC distributions of the 110 Staphylococcus aureus were estimated, fitted by goodness-offit test and Non-Linear Least Squares Regression(NLSR) for establishment of wildtype breakpoint(COWT). The MIC range were 0.03-2 μ g/mL and the ECV was thus 2 μg/ml.On the basis of the above study, pharmacokinetic-pharmacodynamics model was established to simulate the efficacy of Cefquinome for different dosage regimen. A dosage of 2 mg/kg every 12 h for 3 days was expected to reach a bactericidal activity against S. aureus in case of septicemia. Such a value of 50 % of time above the MIC. As 0.5 μ g/ml covers 95 % of your MIC distribution. This will provide criteria control for the usage and monitoring resistance of Cefquinome in cattle. |
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