Single‐dose pharmacokinetics of flumequine in cod (Gadus morhua) and goldsinny wrasse (Ctenolabrus rupestris)

Abstract

Knowledge of the pharmacokinetic properties of drugs to combat bacterial infections in cod (Gadus morhua) and wrasse (Ctenolabrus rupestris) is limited. One antimicrobial agent likely to be effective is flumequine. The aim of this study was to investigate the pharmacokinetic properties of flumequine in these two species. Flumequine was administered intravenously to cod (G. morhua) at a dose of 5 mg/kg bodyweight and wrasse (C. rupestris) at a dose of 10 mg/kg. Flumequine was also administered orally to both species at a dose of 10 mg/kg body weight, and as a bath treatment at a dose of 10 mg/L water for 2 h. Identical experimental designs were used otherwise. The study was performed in seawater with a salinity of 3.2% and a temperature of 8.0 +/- 0.2 degrees C (cod) and 14.5 +/- 0.4 degrees C (wrasse). Pharmacokinetic modelling of the data showed that flumequine had quite different pharmacokinetic properties in cod and wrasse. Following intravenous administration, the volumes of distribution at steady-state (Vss) were 2.41 L/kg (cod) and 2.15 L/kg (wrasse). Total body clearances (Cl) were 0.024 L/hxkg (cod) and 0.14 L/hxkg (wrasse) and the elimination half-lives (t1/2lambda z) were calculated to be 75 h (cod) and 31 h (wrasse). Mean residence times (MRT) were 99 h (cod) and 16 h (wrasse). Following oral administration, the t1/2 lambda z were 74 h (cod) and 41 h (wrasse). Maximal plasma concentrations (tmax) were 3.5 mg/L (cod) and 1.7 mg/L (wrasse), and were observed 24 h post-administration in cod and 1 h post-administration in wrasse. The oral bioavailabilities (F) were calculated to be 65% (cod) and 41% (wrasse). Following bath administration, maximal plasma concentrations were 0.13 mg/L (cod) and 0.09 mg/L (wrasse), and were observed immediately after the end of the bath.

Efficacy of orally administered flumequine in the treatment of vibriosis caused by Listonella anguillarum in Atlantic cod Gadus morhua

“…Tissue and plasma analysis showed that flumequine was readily absorbed and distributed from plasma to tissues (Table 1). This confirmed the results obtained by Hansen & Horsberg (2000), who calculated the volume of distribution (V d ) of flumequine in cod to be 2.4 l kg -1 following a single bolus intravenous administration. In the same study, a plasma C max of 3.5 µg ml -1 was found 24 h after a single oral administration of 10 mg kg -1 body weight.…”

“…In that respect several authors, including the corresponding author of this paper, related pharmacokinetic data of antibacterial agents in fish to the assumptions by Stamm (1989) and Shojaee AliAbadi & Lees (2000) with the aim of predicting clinical outcome of the treatment. Taking the plasma C 24 concentrations found in this study, a MIC value of 0.015 µg ml -1 determined by Samuelsen & Lunestad (1996) and a calculated AUC value of 533 mg h l -1 for flumequine in cod (Hansen & Horsberg 2000) in combination with the statements by Stamm (1989) and Shojaee AliAbadi & Lees (2000), it can be shown that all the doses of flumequine used in the present study fulfil the criteria (Table 1). A plot of the mean plasma concentrations against doses, excluding the 10 mg dose, shows a linear relationship (Fig.…”

“…The minimum inhibitory concentration (MIC) value for the pathogen was determined to be 0.015 µg ml -1 (Samuelsen & Lunestad 1996). An area under curve (AUC) value of 533 mg h l -1 from Hansen & Horsberg (2000) was used were statistically equivalent in efficacy. However, the data set suggests that a daily dose of 25 mg is needed to obtain the desired effect.…”

“…The C max values for the various doses therefore need to be determined. On the basis of the available data on the single-dose pharmacokinetics of flumequine in cod (Hansen & Horsberg 2000), presenting a T max (time to reach C max ) of 24 h in plasma, it can be argued that C 24 (the concentration measured 24 h following last medication) is a reasonable proxy for C max in cod.…”

“…Oxolinic acid has been the agent of choice in treating vibriosis in cod but medication has been based on doses and dose regimes originally intended for Atlantic salmon Salmo salar. Recent studies have revealed that oxolinic acid, florfenicol and flumequine all possess excellent pharmacokinetic properties in cod (Hansen & Horsberg 2000, Samuelsen et al 2003a, and have demonstrated high efficacy of oxolinic acid and florfenicol against experimentally induced vibriosis (Samuelsen & Bergh 2004). However, no study of the efficacy of flumequine in treating vibriosis in cod has been published.…”