Assessing the effect of therapeutic level of oxytetracycline dihydrate on pharmacokinetics and biosafety in Oncorhynchus mykiss (Walbaum, 1792)

Abstract

Abstract The aim of the experiment was to investigate the pharmacokinetics of oxytetracycline dihydrate after a single oral administration of 80 mg kg−1 day−1 in rainbow trout and assess its biosafety at concentration of 80, 240, 400, and 800 mg kg−1 day−1 over 30 days, focusing on various aspects such as effective feed consumption, physiological responses, drug tolerance, and detection of low drug concentrations in rainbow trout. The pharmacokinetics study spanned a duration of 5 days, while the assessment of biosafety extended for a 30-day safety margin, followed by a subsequent 10-day residual analysis. Pharmacokinetic analysis revealed slow absorption with low-rate constant in tissues. Absorption rates vary among tissues, with the gill showing the highest rate (0.011 h−1) and plasma exhibiting the slowest (0.0002 h−1). According to pharmacokinetic analysis, the highest concentration, Cmax (µg kg−1) was observed in the kidney (9380 µg kg−1) and gill (8710 µg kg−1), and lowest in muscle (2460 µg kg−1). The time (Tmax) to reach peak concentration (Cmax) varied among tissues, ranging from 3 h in the gill to 32 h in the muscle, with 24 h in plasma, 32 h in the kidney, and 16 h in both the liver and skin. The liver and kidney had the highest area under the concentration-time curve (AUC(0−128)), indicating widespread drug distribution. Prolonged elimination occurred at varying rates across tissues, with the gill showing the highest rate. The study found that OTC concentrations exceeded the LOD and LOQ values. Biosafety evaluation showed effective feed consumption, physiological responses, and low drug concentrations in muscle at the recommended dosage of 80 mg kg−1 fish day−1.

Keywords

• Oxytetracycline dihydrate
• Rainbow trout
• Drug absorption kinetics
• Antibiotic residue
• Non-compartmental analysis