Pharmacokinetics of oxolinic acid in gilthead sea bream, Sparus aurata L.

Abstract

This is the first study on the pharmacokinetic parameters of oxolinic acid (OA) in gilthead sea bream, Sparus aurata L. The kinetic profile of OA was studied after a single intravascular injection (20 mg kg−1) in 100 g fish at 20 °C. The distribution half‐life (t1/2α) and the elimination half‐life (t1/2β) of the drug were found to be short (0.51 and 12.60 h, respectively). The drug penetration from the plasma to the tissues was adequate as the apparent volume of distribution of the drug at steady‐state (Vd(ss)) was found to be 2.11 L kg−1. The mean residence time (MRT) of OA was short (14.25 h) and the total clearance rate (ClT) of the drug was low (0.15 L kg−1 h−1). The bioavailability (F %) of OA following oral administration (30 mg kg−1) was also low (14%). Maximum values were observed for muscle at 0.5 h after injection, with levels declining as with subsequent sampling. At the first two time points (0.5 and 1 h) plasma levels of OA were higher than muscle, however, the reverse was evident for subsequent samples. Following oral administration, highest muscle levels were found at 16 h and, with the exception of the 24‐h sampling, muscle OA concentrations were higher than plasma at all time points. The fast elimination of OA suggests short withdrawal times with reference to human consumption of treated fish.

A single‐dose pharmacokinetic study of oxolinic acid and vetoquinol, an oxolinic acid ester, in cod, Gadus morhua L., held in sea water at 8 °C and in vitro antibacterial activity of oxolinic acid against Vibrio anguillarum strains isolated from diseased cod

“…1993; Martinsen & Horsberg 1995; Samuelsen et al. 2000), 28% in turbot, Scophthalmus maximus (L.), (Poher & Blanc 1998) and only 15% in Atlantic halibut (Samuelsen & Ervik 1999) and 14% in gilthead sea bream, Sparus aurata L. (Rigos, Alexis, Tyrpenou, Nengas, Piper & Troisi 2002). The gain in bioavailability of oxolinic acid by administrating vetoquinol was lower in cod (55 vs. 72%) than in Atlantic salmon (25 vs. 71%) and Atlantic halibut (15 vs. 64%) (Samuelsen & Ervik 1999; Samuelsen et al.…”

Antibacterial Agents in Mediterranean Finfish Farming: A Synopsis of Drug Pharmacokinetics in Important Euryhaline Fish Species and Possible Environmental Implications

“…Maximal plasma OA levels following single or multiple oral dosing in both gilthead and sharpsnout sea bream, were found to be $1 lg mL )1 (Rigos et al, 2002c(Rigos et al, , 2003b(Rigos et al, , 2004d, while respective values for FLU after single dosing in gilthead sea bream was higher at 1.7 lg mL )1 . This difference may be attributable to the greater F of FLU in gilthead sea bream, and is therefore indicative of the greater therapeutic efficacy of FLU as previously mentioned.…”

“…However, OA absorption studies in European sea bass and sparids have revealed relatively high apparent digestibility (absorption) values (64-92%) (Rigos et al, 1999(Rigos et al, , 2002d. In contrast, F for OA in sparids is surprisingly low (14-15%) (Rigos et al, 2002c(Rigos et al, , 2004d, indicating that complexing of OA with cations reduces its membrane permeability and is indicative of significant first pass elimination following absorption. On the contrary, FLU has been shown to be more bioavailable than OA in gilthead sea bream (29%) .…”

“…Although the penetration of intravascularyinjected OA in the tissue compartment of euryhaline fish is moderate (V d(ss) =2.1-2.6 L kg )1 ) (Poher et al, 1997;Rigos et al, 2002cRigos et al, , 2004d it is higher than that of FLU (0.6-1.5 L kg )1 ) (Rigos et al, 2002e, 2003c. A study of the tissue distribution of OA following multiple dosing, revealed that liver, bile and skin act as reservoirs of the drug treatment in both gilthead and sharpsnout sea bream with rapid depletion of the drug from all tissues to ''consumer safe levels'' (MRL = 100 ng g )1 ; EMEA, 2003) 24 h after completion of treatment at 19°C (Rigos et al, 2003b).…”

The kinetic profile of oxolinic acid in sharpsnout sea bream, Diplodus puntazzo (Cetti 1777)

“…The tissue distribution and residue depletion of OA following multiple in‐feed dosing was recently studied in sharpsnout sea bream (Rigos, Nengas, Alexis, Tyrpenou & Troisi 2003). Information on the kinetic profile of OA became also available for the most important farmed sparid, gilthead sea bream, which is much more closely related to sharpsnout sea bream (Rigos, Alexis, Tyrpenou, Nengas, Piper & Troisi 2002a). However, the pharmacokinetics of OA may differ between the two sparids as was seen previously in between other fish species (Kleinow, Jarboe, Shoemaker & Greenless 1994) and bioavailability of the drug has not been addressed yet in sharpsnout sea bream.…”