Oral pharmacokinetic profile and withdrawal time estimation for tylosin tartrate in the cultured olive flounder Paralichthys olivaceus

Abstract

The Korean government regulates pharmaceutical parameters and withdrawal times for antimicrobials in aquaculture. Tylosin tartrate (TT) is a bacteriostatic antibacterial agent mainly used in veterinary medicine for the prevention and treatment of gram-positive bacterial infections. However, pharmacokinetic (PK) and drug withdrawal reports in aquatic animals, including olive flounder (Paralichthys olivaceus), are limited. This study aimed to determine the PK profile and drug withdrawal time following oral TT administration (10 or 20 mg/kg) in olive flounder. The concentrations of tylosin in the serum and muscle plus skin were analyzed using liquid chromatography and tandem mass spectrometry. PK parameters were calculated for serum samples using the PKSolver software based on a non-compartmental model. The PK parameters after a single oral dose of 10 (or 20) mg/kg were as follows: Cmax, 0.7 (1.49) μg/mL; Tmax, 12 h; t1/2, 22.83 (19.44) h; area under the concentration curve, 10.58 (33.17) μg/mL h; and mean residence time, 20.53 (25.62) h. Oral administration of TT at a dose of 10 mg/kg at 24–48 h intervals may help achieve efficacy comparable to that obtained with antimicrobials at minimum inhibitory concentration values of ≤ 1 μg/mL. After a 5-day oral administration of TT in olive flounder (water temperature, 22 ℃), a withdrawal time of 17.8 (rounded up to 18 days) days was required to achieve muscle plus skin TT residue levels below 100 μg/kg, which is the European limit; the corresponding value at a lower water temperature (13 ℃) was 20 days. Overall, this study not only serves as a reference for authorizing the clinical use of TT in olive flounder but also provides valuable data for evaluating the safety of food derived from aquatic animals.

Keywords

• Olive flounder
• Pharmacokinetics
• Residue depletion
• Tylosin tartrate
• Withdrawal time