The aim of this study was to carry out a pharmacokinetic (PK) study of oxytetracycline (OTC) in rainbow trout using different routes of administration, different doses, diploid and triploid fish and two temperature conditions (10°C vs 16°C). Method: A total of 216 ( 310 +/- 37 g at the start of the experiment) fish were used, divided into 24 tanks of 9 individuals. The trial was carried out cross-over, with each fish receiving the drug by vein and orally, by gavage or by spontaneous intake via a coating of the antibiotic on the feed, at 2 distinct temperatures, 10 and 16°C. A one-month wash-out period was observed between each administration. Each fish, for each modality, was sampled 3 or 4 times over a period of 11 days, to establish its individual PK profile. Samples of coated feed and plasma were assayed using a sensitive HPLC-MS/MS method. The plasma data obtained were analysed using population pharmacokinetic (pop PK) modelling to estimate major PK parameters and assess the influence of covariates such as weight or ploidy (diploids vs. triploids). Results: Actual antibiotic concentrations in feed were significantly lower than the theoretical target concentrations (up to 40%). In addition, by comparing the pharmacokinetic data from gavage with those from spontaneous intake, an estimate of leaching (loss of drug when the feed is immersed in water) was obtained. A bi-compartmental model best described the data. The absolute oral bioavailability of oxytetracycline appears to be very low (less than 3%). Oxytetracycline is eliminated very slowly, and the clearance was highly affected by the water temperature (elimination half-life approximately 87h at 16°C vs 120h at 10°C). Weight was positively correlated with clearance, as was triploidy, but to a lesser extent. Based on the final popPK model and the targeted value of the PKPD index fAUC/MIC, Monte Carlo simulations are currently carried-out to predict the PKPD breakpoint to treat A. salmonicida