Evaluation of serum florfenicol concentrations and PK/PD ratios in pigs following In-Feed administration at four dose levels
DOI:
https://doi.org/10.17533/udea.rccp.e360197Keywords:
dose level, feed, florfenicol, pharmacokinetics and pharmacodynamics (PK/PD), pigsAbstract
Background: Florfenicol treatment is often necessary in intensive swine clinics, and appropriate dosing should be followed. However, the pioneer manufacturer's original registration stated that the dose could be set at 40 ppm as in feed medication. Other generic brands have established other doses (80, 100, and 200 ppm). Objective: This trial aimed to assess the PK/PD rationale of the referred doses, and determine the serum concentrations of florfenicol achieved in pigs after dosing them in feed and ad libitum with florfenicol at four different dose levels: 40, 80, 100, and 200 ppm. Then, the pharmacokinetics/pharmacodynamics ratios are established. Methods: Through HPLC, serum concentrations of florfenicol achieved in Landrace/Duroc spayed pigs weighing approximately 10 kg were determined. Medicated feed was administered ad libitum. The selected in feed concentrations were 40, 80, 100, and 200 ppm. Considering the farm-established feed intake of 4% of their body weight, doses achieved were: 1.6, 3.2, 4, and 8 mg/kg, respectively. Only florfenicol was determined through a chromatographic method. Monte Carlo simulations were carried out. Results: As expected, there are significant differences when comparing the mean serum concentrations of florfenicol achieved with each dosage level of the antibacterial drug. Since florfenicol is considered a time-dependent antibacterial and, as established in the literature, is only 15% bound to plasma protein in pigs, Monte Carlo simulations were based on 85% of the serum concentrations reached with each dose. Based on the available literature, target attainment was set either at MIC0.4 µg/mL or MIC2.0 µg/mL, and %T to reach those values within the dosing interval (DI) was set at 100%, i.e., 24 h. The 40-ppm dose only achieves 14 h of useful concentrations (%T ≥ MIC0.4 µg/mL = 58% of the DI). The 100 to 200 ppm doses achieved %T ≥ MIC0.4 µg/mL = 100% of the DI. The %T reaching MIC2.0 µg/mL was only possible with 200 ppm, achieving 95% of the DI, while the 100 ppm dose achieved only 70.8% of the DI. As metaphylactic treatment is often necessary in intensive swine farms, and florfenicol should only be administered when a given pathology has been proven, the 40-ppm dose resulted unsuitable, while 100 and 200 ppm appear to be acceptable, and the 80 ppm marginally acceptable for susceptible pathogens.
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