Pharmacokinetics, pharmacodynamics and withdrawal time of doxycycline in white leg shrimp (Litopenaeus vannamei) after oral administration.

This research aimed to investigate the pharmacokinetics (PK), withdrawal time (WT) and hepatopancreas histological impact of doxycycline (DOX) in white leg shrimp (Litopenaeus vannamei). To determine PK parameters in hemolymph, hepatopancreas, and muscle, a single oral dose of 20 mg DOX/kg body weight was administered, following by interval sampling during 24 h. DOX concentrations were quantified by high-performance liquid chromatography coupled with tandem mass spectrometry, and PK parameter estimation was done using a one-compartmental model. The maximum concentrations in shrimp hemolymph, hepatopancreas and muscle were 1.09 µg/mL, 2.37 µg/g and 0.46 µg/g at 1.6 h, 0.23 h and 2 h, respectively. The pharmacokinetics/pharmacodynamics (PK/PD) properties were integrated based on the concentration-time curves of DOX in the hepatopancreas over the minimum inhibitory concentration (MIC) of DOX against V. parahaemolyticus. It was indicated that the time during which the DOX concentration in the hepatopancreas was above the MIC (T > MIC) was approximately 4 h, corresponding theoretically to an 8-hour dosing interval. However, this PK/PD interpretation is presented as supportive information and should be interpreted with caution. A depletion study was conducted by administering DOX-medicated feed once and twice daily for three consecutive days at the same dose. DOX residues in shrimp muscle dropped below the limit of detection after 14 days of stopping medication. Based on a maximum residue limit (MRL) of 50 µg/kg, the estimated withdrawal time at 26.5 °C ranged from 8 to 10 days, depending on the dosing regimen (once or twice a day). Regarding histological analysis, the effect of DOX on hepatopancreas was significant during the twice a day dosing treatment, but recovery of hepatopancreatic cells was observed within seven days after medication.