Studies on Pharmacokinetics/Pharmacodanymics of Enrofloxacin in Broiler chicken

Abstract

Enrofloxacin(ENR) is a synthetic and second generated fluoroquinolone antibiotics, and has been showed broad spectrum antimicrobial activity. The mechanism of action of ENR is known that inactivation of DNA gyrase by interfering DNA synthesis. It is widely used in veterinary medicine in cattle, dogs, poultry, fish, and cats to treat diseases caused by various bacteria. It is reported that ENR sales amount is the highest among all of antibiotics used in chicken in Korea several years.In this study, pharmacokinetic(PK) and pharmadynamic (PD) of ENR administered with PO and IV were carried out to understand pharmacology of ENR in chicken. To analyze PK parameters, sensitive detection method for ENR was developed and validated by liquid chromatography tandem mass spectrometry, and its metabolite ciprofloxacin in broiler chicken plasma, which was further analyzed to study the pharmacokinetics in broiler chicken. Animal study was carried out in chicken and ENR was administered with PO and IV routes with 10 mg/kg. Serum samples were taken for 20 times. The serum samples were treated for chromatography analysis. The LC‐MS/MS analysis was carried out mobile phase gradient consisting 0.1 % formic acid in D.W. (A) and 0.1 % formic acid in ACN (B) with C18 reverse phase column. Mass spectrometry was performed using the positive ion mode and the selected ion monitoring (MRM). The methods validation results showed that good linearity (R2>0.999) and the quantified average recovery of ENR was 99% at level of 10 ng g−1 ~100 ng g−1. The percent of coefficient of variation (CV) for the described method was less than 5.1 % over the range of concentrations. The limits of detection (LOD) and quantification (LOQ) were 5 and 15 ng g−1, respectively. Several PK parameters of ENR those are area under the curve (AUC), half‐life (T1/2), peak plasma concentration (C max) and so on were obtained from LC‐MS/MS analysis.PD analysis was carried using in vitro (MIC) and ex vivo (time‐kill assay). On MIC studies, ENR(0.004~32 ug/ml) was incubated sensitive bacteria and the MIC concentration was determined by visible turbidity in incubation tubes. The ex vivo study was carried using serum samples which containing ENR from chicken. Integrated PK/PD analysis was carried out based on each PK and PD data. Based on PK/PD analysis, the resistance of ENR on chicken is very high on target bacteria such Campylobacter jejuni, we suggest that newly establishment of administration of ENR in broiler chicken.Support or Funding InformationThis research was supported by a fund(B‐1543073‐2015‐17‐01) by Research of Animal and Plant Quarantine Agency, South Korea