Hepatopancreatic and muscular distribution of oxytetracycline antibiotics in farmed pacific white shrimp (Penaeus vannamei): a physiological-based pharmacokinetic model approach

摘要

Oxytetracycline (OTC) pharmacokinetic models previously used to investigate Penaeus vannamei have not addressed the specific problems related to drug distribution/disposition in particular tissues. This study aimed to provide an insight into OTC kinetics in the hepatopancreas and muscle based on a physiological model approach. Adult male P. vannamei at the C-D inter-moulting stage were randomly assigned to intra-sinus and oral administrations. In the intra-sinus group, shrimps were dosed via the ventral sinus at an OTC level of 10.0 og gp# body weight, while in the oral one, they were force fed at a dose level of 50.2 og gp#. The medicated animals were sampled at various time intervals until 170 h after dosing. Haemolymph, muscle and hepatopancreas samples were taken and OTC levels were determined using the validated HPLC method. A model focused on the hepatopancreas and muscle was developed. Oxytetracycline pharmacokinetic profiles in particular tissues were fitted into the model with an Rpo of between 0.6568 and 0.9904. Oxytetracycline muscular distributions were essentially identical for both groups and the drug did not accumulate in muscle. The distributions in the hepatopancreas for both groups were extensive, whereas that for oral administration was approximately 2.3 times greater than that for the intra-sinus one. It was demonstrated that hepatopancreatic OTC may undergo significant first-pass elimination with non-linear kinetics.