Pharmacokinetics and residue depletion of erythromycin in rainbow trout Oncorhynchus mykiss (Walbaum)

Abstract

Erythromycin (ERY) is a drug active against Gram-positive bacteria such as Lactococcus garvieae, a pathogen responsible for an important disease that may cause a substantial decrease in rainbow trout Oncorhynchus mykiss (Walbaum) production, the species of fish most commonly produced in Italy. In the literature, studies on the kinetics behaviour of ERY in fish are limited. Therefore, the aim of the present study was to evaluate the pharmacokinetics of ERY in rainbow trout after a single oral treatment with 75 mg kg⁻¹ body weight (b.w.) of ERY and the residue depletion after multiple oral administration of 75 mg kg⁻¹ b.w. day⁻¹ of ERY for 10 days. Blood concentrations of ERY increased up to 20.24 ± 13.32 μg mL⁻¹ at 6 h, then decreased to 5.97 ± 3.89 μg mL⁻¹ at 24 h. The time during which the antibiotic remains in the bloodstream at concentrations exceeding the MIC (T > MIC) and the area under the serum concentration-time curve (AUC)/MIC are both pharmacokinetic-pharmacodynamic (PK/PD) predictors of ERY efficacy, and the data obtained allowed us to hypothesize that a dosage of 75 mg kg⁻¹ b.w. day⁻¹ of ERY could treat the lactococcosis in trout. Regarding the study of ERY depletion, rapid elimination was observed in tissue (muscle plus adherent skin); in fact the concentrations were below the limit of quantification in all samples (except two) by day 10 post-treatment. ERY is not licensed in Europe for use in aquaculture, and its use is possible only by off-label prescription with a precautionary withdrawal time of 500 degree-days, as established by Directive 2004/28/EC. From the data obtained in this study, a withdrawal time of 8.90 days was calculated, corresponding, in our experimental conditions, to 117.5 degree-days, a value significantly lower than that established by the European directive.

Pharmacokinetics, optimal dosages and withdrawal time of florfenicol in Asian seabass (Lates calcarifer) after oral administration via medicated feed

“…Only partial information of PK and tissue distribution of oxytetracycline, oxolinic acid and sulfadimidine (sulfamethazine) are available so far (Chai‐anan et al, 1993; Chen et al, 2020); PK and tissue depletion characteristics of FF, one of the most popularly used antimicrobials in fish farming, has yet to be evaluated in this fish. The current study found that the serum concentration‐time profile of FF in Asian seabass after administration via medicated feed was best fitted with the one‐compartmental model, which is in line with the general observation that a drug following medicated feed administration is usually best described by the one‐compartmental model (Chen et al, 2005; Di Salvo et al, 2013; Ibrahim et al, 2019; Teles et al, 2016), whereas those after oral gavage of drug solution often best explained by the two‐compartmental model (Hu et al, 2013; Koc et al, 2009; Rairat et al, 2020; Rairat, Liu, et al, 2022; Shan et al, 2020; Zhang & Li, 2007). Following voluntary ingestion of the medicated feed over a certain period of time (usually within a few minutes), drug particle/molecules on the surface of the pelleted feed take time to be released before being absorbed through the fish intestinal epithelium and appearing in the systemic circulation.…”