Population Pharmacokinetics of Enrofloxacin in Micropterus salmoides Based on a Nonlinear Mixed Effect Model After Intravenous and Oral Administration

Abstract

This study aimed to investigate the PPK of EF in largemouth bass after oral and intravenous administration based on a nonlinear mixed effect model. Samples were collected using the sparse sampling method at pre-designed time points determined by high-performance liquid chromatography with a fluorescent detector. The initial PK parameters were estimated by reference search and the calculation of a naïve pooled approach. The covariate model included a variation in body weight. The oral dose data were best fitted by a one-compartment model. The injection dose data were best fitted by a two-compartment model. The results demonstrated that body weight had no marked effect on the parameters of PPK. Finally, the bioavailability was calculated to be 12.24%. The area under the concentration-time curve/minimum inhibitory concentration was estimated to be ≥408.16, indicating that EF at 20 mg/kg has high effectiveness for aquatic pathogens.

Keywords: body weight; enrofloxacin; largemouth bass; population pharmacokinetics; statistical approaches.

Figure 1

(A): Plot of conditional weighted residual values (CWRES) versus time after oral dose (TAD); (B): logarithmic plot of the dependent variable (DV) versus individual predicted plasma concentrations (IPRED) of enrofloxacin in all experimental animals; (C): logarithmic plot of the dependent variable (DV) versus predicted plasma concentrations (IPRED) of enrofloxacin in all experimental animals.

Figure 2

(A): Plot of conditional weighted residual values (CWRES) versus time after intravenous dose (TAD); (B): logarithmic plot of the dependent variable (DV) versus individual predicted plasma concentrations (IPRED) of enrofloxacin in all experimental animals; (C): logarithmic plot of the dependent variable (DV) versus predicted plasma concentrations (IPRED) of enrofloxacin in all experimental animals.