G Troisi

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

The literature pertaining to the use of registered antibacterial agents in Mediterranean finfish farming is reviewed, with an emphasis on the Greek fish-farming industry. This review provides a scientific resource dedicated to the design of future antibacterial dosing regimes in Mediterranean fish farming, where insufficient supporting information is currently available. This paper addresses the paucity in knowledge concerning pharmacokinetics and the efficacy and environmental impact of commonly used antibacterials needed to direct future research and promote good practices in the euryhaline fish farming industry. Several registered antibacterials are currently available for combating bacterial infections, including tetracyclines, (fluoro) quinolones, potentiated sulfa, penicillin and chloramphenicol derivatives. Based on the available data, oxytetracycline (OTC) and quinolone drugs (oxolinic acid – OA and flumequine – FLU) are the most widely used in Mediterranean aquaculture. As a result these drugs have received the most extensive studies, whereas, there is considerable paucity of reliable data on pharmacokinetic and the depletion characteristics of other drugs used, particularly potentiated sulfa, penicillin derivatives and florfenicol. We find there is incomplete data on drug efficacy and minimum inhibitory concentrations (MIC) for common antibacterials used against the major bacterial pathogens of Mediterranean fish species. Furthermore, a considerable lack of data on environmental drug concentrations around Mediterranean fish farms was also identified, highlighting the need for more extensive environmental studies to monitor contamination in environmental components i.e., water and sediment, and in non-target species (flora and fauna). Prudent selection and use of antibacterials can encourage lower dosage applications, enhance treatment efficacy, and help to minimize contamination of the environment. Selection of readily bioavailable drugs which have low environmental persistence, low aquatic toxicity and high antibacterial efficacy is advised, to reduce potential losses to the environment and associated toxic effects on target species and the development of bacterial resistance. Lack of present data made it impossible to provide thorough and accurate guidance on selection and use of antibacterials and approaches for minimizing environmental impacts for the treatment of major euryhaline aquaculture species.

Bioaccumulation of polychlorinated biphenyls (PCBs) and dichlorodiphenylethane (DDE) methyl sulfones in tissues of seal and dolphin morbillivirus epizootic victims

Polychlorinated biphenyl (PCB) and dichlorodiphenylethane (DDE) methyl sulfone (MSF) metabolites possess high affinities for binding two homologous 16,000 Da homodimeric receptor proteins in the lung (Clara cell secretory protein, CCSP) and the uterus (uteroglobin, UG), leading to selective bioaccumulation of MSFs in these tissues. As marine mammals are highly exposed to organochlorines, concentrations of PCBs, PCB MSFs, DDT, and DDE MSF were analyzed in blubber, lung, and uterus samples from harbor seal (Phoca vitulina) and striped dolphin (Stenella coeruleoalba

Pharmacokinetics and bioavailability of oxytetracycline in gilthead sea bream (Sparus aurata) after a single dose

Abstract This is the first study to investigate the pharmacokinetic parameters of oxytetracycline (OTC) in gilthead sea bream ( Sparus aurata ). Following a single intravascular injection of OTC (40 mg/kg) in 100 g fish kept at 20 °C, the distribution half-life ( t 1/2 α ) and the elimination half-life ( t 1/2 β ) of OTC were found to be long (2 and 53 h, respectively). The drug was well distributed throughout the internal body compartments since the apparent volume of distribution of the drug at steady-state ( V d(ss) ) and the apparent volume of distribution by the area method ( V d(area) ) were found to be high (2.9 and 3.8 l/kg, respectively). OTC had a long mean residence time (MRT) (56 h) but a short total clearance (CL T ) (0.05 l/kg h). The slow elimination of the drug suggests a need for long withdrawal periods prior to use of dosed fish for human consumption. Although the bioavailability ( F %) of OTC following oral administration in aqueous suspension (75 mg/kg) was calculated to be low (9%), maximum OTC plasma concentration was relatively high (2.5 μg/ml), indicating that current therapeutic regimens applied to gilthead sea bream might be effective against bacterial pathogens.

Tissue distribution and residue depletion of oxolinic acid in gilthead sea bream (Sparus aurata) and sharpsnout sea bream (Diplodus puntazzo) following multiple in-feed dosing

Abstract The tissue distribution and residue depletion of oxolinic acid (OA) were investigated in gilthead sea bream and sharpsnout sea bream after a multiple (10 days) in-feed administration (30 mg/kg fish) at 19 °C. Plasma, muscle, skin, liver and bile were sampled daily during treatment (1–10 days) and post-treatment (11,12, 14, 15 and 17 days) and subsequently analysed for OA concentrations using high-performance liquid chromatography and fluorescent detection (HPLC-SFD). Oxolinic acid displayed biphasic elimination in tissues of both species during treatment and reached “consumer safe levels” 24 h after treatment. OA concentration in gilthead sea bream peaked on day 4, with highest concentrations in liver (2660 ng/g), followed by bile (2370 ng/ml), skin (2350 ng/g), muscle (1330 ng/g) and plasma (880 ng/ml). In sharpsnout sea bream, peaked OA concentrations were observed in liver (2720 ng/g) on day 4, while highest concentrations were measured later on day 5 in plasma (910 ng/ml) and day 6 in bile (2360 ng/ml), skin (1960 ng/g) and muscle (1770 ng/g). The calculated areas under the concentration curves (AUC) also reflect a good tissue distribution of OA. Elimination half-lives ( t 1/2 ) were estimated to be 11–14 and 11–19 h in tissues of gilthead sea bream and sharpsnout sea bream, respectively. Multiple dosing of OA in sparids should be adequate to confront bacterial pathogens considering published minimum inhibitory concentrations of the drug.

PCB-ASSOCIATED ALTERATION OF HEPATIC STEROID METABOLISM IN HARBOR SEALS (Phoca vitulina)

Hepatic cytochrome P-450 (CYP450) isozymes are involved in xenobiotic detoxification and steroid metabolism. Seals are highly exposed to polychlorinated biphenyls (PCBs) in the environment, resulting in CYP450 induction, which may have concomitant effects on CYP450 steroid metabolism. Experiments were conducted to determine rates of steroid metabolism in harbor seal (Phoca vitulina