A physiologically based pharmacokinetics model for florfenicol in crucian carp and oral‐to‐intramuscular extrapolation

Abstract

In this study, an oral physiologically based pharmacokinetics (PBPK) model was developed for florfenicol in crucian carp (Carassius auratus). Subsequently, oral-to-intramuscular extrapolation was performed and the two models were used to predict florfenicol concentrations in the edible tissues of crucian carp. The oral model gave good predictions in most tissues, except for kidney and liver in which the florfenicol concentrations were underestimated at the later time points. In contrast, using the intramuscular model, the concentrations in the kidney were overestimated at the later time points. Both models had the best predictive ability in the main edible tissue, the muscle. The oral model also accurately predicted the florfenicol concentrations in the muscle after multiple doses. The present study demonstrated the feasibility of predicting florfenicol concentrations in the edible tissues of crucian carp using a route-to-route extrapolation method.

Estimating danofloxacin withdrawal time in broiler chickens based on physiologically based pharmacokinetics modeling

“…It is important to note that the steady‐state concentrations were attained following administration via the drinking water, while in the present model, danofloxacin was administrated by oral gavage. However, our previous study (Yang et al ., ) had shown that there were few differences in the P X s for a compound after different routes of administration in a particular species. In addition to these parameters mentioned previously, other parameters, such as partition coefficient of the ‘rest’ ( P r ), Cl re , Cl he , K a , and K gic were optimized using a maximum likelihood algorithm (Nelder–Mead) provided by the software of acslXtreme based on the plasma concentrations of danofloxacin after one single oral dose (Knoll et al ., ).…”

“…In recent years, there has been an increase in the use of physiologically based pharmacokinetics (PBPK) model to estimate xenobiotics residue (Buur et al ., ; Yuan et al ., ; Leavens et al ., ; Yang et al ., , ,b, ,b). A PBPK model is a body composed of compartments, and each compartment contains mathematical equations describing the chemical's absorption, distribution, metabolism, and elimination (ADME).…”

“…A PBPK model is a body composed of compartments, and each compartment contains mathematical equations describing the chemical's absorption, distribution, metabolism, and elimination (ADME). Compared with conventional allometry and compartmental models, PBPK models are able to provide quantitative means of extrapolating ADME across routes of administration (Yang et al ., ) and species (Yuan et al ., ) or from healthy adults to diseased ones (Li et al ., ). The difference lies in its ability to substitute species‐specific physiological, anatomical, and biochemical parameters into the PBPK model and to extrapolate across dosing regime and species.…”

Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits

“…In recent years, there has been an increase in the applications of physiologically based pharmacokinetic (PBPK) models to predict veterinary drug residues (Huang et al., ; Li, Gehring, Riviere, & Lin, ; Yang, Huang, et al., ; Yang et al., ; Yang, Sun, Liu, & Zeng, ; Yang, Sun, et al., ; Yang et al., ; Zeng et al., ). Compared with the traditional monitoring method after animal slaughter, the PBPK model is based on mass‐balance equations defined by physiological mechanisms, and it is predictive in nature and allows for the use of in vitro mechanistic data and population variability data to predict the distribution of drug in animals (Lin, Gehring, Mochel, Lave, & Riviere, ).…”

Pharmacokinetics of florfenicol in blunt‐snout bream (Megalobrama amblycephala) at two water temperatures with single‐dose oral administration

“…Florfenicol (FFC) is the second most frequently used antibacterial agent in Norwegian aquaculture (Samuelsen, Bergh, & Ervik, ). To our knowledge, in Asia, where the vast majority of aquaculture takes place, FFC is extensively used to treat pathogenic bacterial infections in aquaculture (Yang et al, ). As a broad‐spectrum chloromycetin‐series antibiotic, FFC is widely used in veterinary medicine.…”