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

## TL;DR

This study uses population pharmacokinetics to model enrofloxacin's behavior in largemouth bass after oral and intravenous administration.

## Contribution

A novel application of nonlinear mixed effect models to study enrofloxacin pharmacokinetics in fish using sparse sampling.

## Key findings

- Oral EF data fit a one-compartment model, while intravenous data fit a two-compartment model.
- Body weight had no significant effect on pharmacokinetic parameters.
- EF at 20 mg/kg showed high effectiveness against aquatic pathogens with an area under the curve/minimum inhibitory concentration ≥408.16.

## Abstract

Population pharmacokinetics (PPK) is an interdiscipline of pharmacokinetics (PK) and statistics. It reflects the influence of fixed effects and stochastic effects on PK and involves the collection of blood samples using the sparse time points method that solves the problem of insufficient blood volume in fish. Therefore, we tried to simulate the PK parameters of enrofloxacin (EF) in largemouth bass (Micropterus salmoides) using the PPK model. This exploration can provide a concise strategy to promote the development of PK methodology for aquatic animals.

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.