Pharmacokinetics of florfenicol in cod Gadus morhua and in vitro antibacterial activity against Vibrio anguillarum

Abstract

The pharmacokinetic profile of the antibacterial agent florfenicol was studied in plasma after intravenous (i.v.) injection and in plasma, muscle and liver following oral (p.o.) administration to cod Gadus morhua, held in seawater at 8°C and weighing 100 to 200 g. Following i.v. injection, the plasma drug concentration-time profile showed 2 distinct phases. The plasma distribution half-life (t 1/2 α) was estimated to be 1.6 h, the elimination half-life (t 1/2 β) to be 43 h, the total body clearance (Cl T ) to be 0.015 l kg -1 h -1 and mean residence time (MRT) to be 74 h. The volume of distribution at steady state, V d(ss) , was calculated to be 1.1 l kg -1 . Following p.o. administration, the bioavailability was estimated to be 91%, the peak plasma concentrations (C max ) to be 10.8 µg ml -1 and the time to peak plasma concentrations (T max ) to be 7 h. Corresponding C max and T max values were 13.0 µg g -1 and 9 h, respectively, in muscle and 12.1 µg g -1 and 9 h, respectively, in liver. The in vitro minimum inhibitory concentration (MIC) values of florfenicol against 3 Vibrio anguillarum strains isolated from diseased cod (A-21, HI-610, HI-618) were 0.5 µg ml -1 for all 3 strains. KEY WORDS: Fish · Pharmacokinetics · Florfenicol Resale or republication not permitted without written consent of the publisherDis Aquat Org 56: [127][128][129][130][131][132][133] 2003 field situation (J. P. Pedersen pers. comm.). After 5 d of treatment daily mortality decreased only slowly and, for this reason, florfenicol was replaced by flumequine, with good results. The in vitro minimum inhibitory concentration (MIC) value for the presumed pathogen against florfenicol was found to be 0.5 µg ml -1. This study was therefore initiated to examine the pharmacokinetic properties of florfenicol in cod, relate the data to the MIC values of bacterial strains isolated from diseased cod and other fish pathogenic bacteria, and evaluate the need for adjustment of the dosage regime. The drug was administered by i.v. injection and incorporated in feed for p.o. administration. MATERIALS AND METHODSChemicals. The Directorate of Fisheries, Department of Quality Control (Bergen, Norway) supplied florfenicol and florfenicol amine standards. Thiamphenicol was obtained from Sigma Chemical and metomidate from Norsk Medisinaldepot. 1-Heptane sulphonic acid was from Fluka Chemie, whereas acetonitrile, methanol (high performance liquid chromatography [HPLC]-grade), phosphoric acid (H 3 PO 4 ), disodium hydrogen phosphate (Na 2 HPO 4 ), trisodiumphosphate (Na 3 PO 4 ), 5-sulphosalicylic acid, hydrochloric acid (HCl), tris(hydroxymethyl)-aminomethan (TRIS), triethylamine and potassium hydroxide (KOH) (p.a.-grade) were all from Merck. Solid phase extraction columns (SPE) (Bond Elute C-18, 100 mg, 1 ml) were from Varian. Stock solutions of florfenicol, florfenicol amine and thiamphenicol were prepared at a concentration of 0.1 mg ml -1 in methanol and stored at -20°C. Working standards were prepared by dilution from the stock solutions with met...

Antimicrobial susceptibility of Francisella noatunensis subsp. noatunensis strains isolated from Atlantic cod Gadus morhua in Norway

“…noatunensis strains tested in this investigation was 0.5 µg ml , respectively, for the 20 mg kg −1 dose in cod, 24 h following the last application (Samuelsen & Bergh 2004). These values therefore show that, following recommended medication with florfenicol (10 mg kg −1 daily for 10 consecutive days), the mean concentrations in plasma will exceed the MIC value of 0.5 µg ml −1 by a good margin for the entire medication period and have the potential of providing a therapeutic effect (Samuelsen et al 2003b). In comparison, a single dose of 10 mg kg −1 florfenicol to tilapia (Oreochromis niloticus × O. aureus) gave C max concentrations of 4.46 µg ml −1 in plasma, 6.88 µg g −1 in muscle and 5.87 µg g −1 in liver and faster elimination with t 1/2 β values of 10 h in plasma, 11 h in muscle and 14 h in liver (Feng & Jia 2009), which is considerably lower than the values found in cod.…”

Pharmacokinetic Study of Florfenicol in Healthy and Vibriosis-infectedPseudosciaena croceaafter Oral Administration

“…There are some reports of its pharmacokinetics determined in Oncorhynchus mykiss, Piaractus brachypomus, P. crocea, Gadus morhua, Salmo salar, Acipenser baeri, Anguilla anguilla, Tilapia, Silurus asotus, and Crucian carp (Horsberg et al, 1996;Lunden and Bylund, 2000;Samuelsen et al, 2003;Lewbart et al, 2005;Park et al, 2006;Feng and Jia, 2008;Bowser, 2009;Sun et al, 2010;Qin et al, 2010;Xie et al, 2012).…”

gyrA and parC Mutations and Associated Quinolone Resistance in Vibrio anguillarum Serotype O2b Strains Isolated from Farmed Atlantic Cod ( Gadus morhua ) in Norway

“…OA has generally been considered to be an effective compound for treatment of bacterial infections in cod. This may be due to the higher bioavailability of OA in cod than in salmon (16). Currently, only four (effectively) antibiotics are licensed for use in aquaculture in Norway, and two of these are quinolones (OA and flumequine).…”