Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus): establishment of optimal dosage and administration in medicated feed

Abstract

The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was studied after single intravenous (10 mg kg ) and oral (100 mg kg ) administration. The plasma concentration-time data of florfenicol were described by an open one-compartment model. The elimination half-life (t ) was estimated to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h . The apparent volume distribution (V ) was calculated to be 0.86 L kg and the mean residence time (MRT ) was 30.2 h. Following oral administration, the maximum plasma concentration (C ) of 55.4 μg mL was reached at 12 h (T ). The absorption constant (k ) was 0.158 h . The bioavailability was estimated to be 57.1%. The low bioavailability observed at higher doses was explained by the saturation of the mechanisms of absorption. The drug absorption process was limited by its inherent low solubility, which limited the amount of available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic data, an optimal dosing schedule for FF administration is hereby provided. Based on the minimum inhibitory concentration found for susceptible strains of Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg FF kg , followed by 6 maintenance doses at 18 mg kg /daily could be effective against furunculosis in turbot.

Preparation, characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot‐melt extrusion technology

“…However, the traditional oral administration preparations of FF are granules, powders, and premixtures, most of which are physical mixtures prepared by combining ordinary excipients such as starch or glucose with the API (FF). Additionally, the APIs are partly degraded by gastric acid, contributing to low bioavailability (57.1% in turbot (Ocenda et al., ), 65.19% in goat (Atef, El‐Gendi, Amer, & El‐Aty, ), and 72.4% in pig (Zhang et al., ). The bioavailability of FF in vivo is considerably reduced because of poor solubility, gastric acid degradation, and unsteady absorption (Nagata & Saeki, ).…”

“…Additionally, the APIs are partly degraded by gastric acid, contributing to low bioavailability (57.1% in turbot (Ocenda et al, 2016), 65.19% in goat (Atef, El-Gendi, Amer, & El-Aty, 2010), and 72.4% in pig (Zhang et al, 2016). The bioavailability of FF in vivo is considerably reduced because of poor solubility, gastric acid degradation, and unsteady absorption (Nagata & Saeki, 1992).…”

Pharmacokinetic–pharmacodynamic modelling for the determination of optimal dosing regimen of florfenicol in Nile tilapia (Oreochromis niloticus) at different water temperatures and antimicrobial susceptibility levels

“…The most likely explanation for the dose‐dependent mismatch between the C min(ss) and target MIC is that non‐linear PK occurred under these circumstances, in which drug metabolism/elimination become saturated such that unexpectedly higher blood concentration was observed. In fact, the PK characteristic of FF in turbot appeared to show non‐linearity when the administered dose was 50 mg/kg or higher (De Ocenda et al, ), possibly due to the saturation of the absorption process (according to the authors). Unfortunately, Equation (3) cannot be applied to determine an optimal dosing regimen at the doses that exhibit non‐linear PK as the calculated dose could be overestimated (higher than the optimum).…”

Non-Selectivity of R-S Media for Aeromonas hydrophila and TCBS Media for Vibrio Species Isolated from Diseased Oreochromis niloticus

“…Bacterial infections represent the major cause of economic losses in fish farms [21]. The recorded mortality in affected farms was 8% to 15% during 2 weeks after disease onset (appearance of clinical signs as daily mortality was 0.5% to 1%) which considered direct economic losses due to bacterial infection.…”