科研之友
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摘要
Toxicokinetics has demonstrated abnormal signs in drug distribution/disposition without waiting until the drug damages the tissues/organs. It is a study of the kinetic assessment of administering high-dose of oxytetracycline (OTC) to white shrimp. Male Penaeus vannamei in the C-D-0 molting stage, were force fed with medicated feeds at various accurate dose levels including 500, 1000, and 2500 mg/kg-body weight (BW). After dosing with different time intervals, hemolymph, muscle, and hepatopancreas were collected, and assayed for OTC by validated high-performance liquid chromatography method. The simulated profile based on the maximum recommended dose was tested to approach the systemic level where the drug was anticipated not to cause significant toxic responses. OTC kinetic profiles in the hemolymph were fitted into the flow limited model having r(2) value between 0.8341 and 0.9373. The relative affinities for the muscle and hepatopancreas changed at dose level exceeding 1000 mg/kg BW. Although hepatopancreatic clearance was non-linearly related with dose, the persistence of OTC in muscle after 2500 mg/kg BW dosing was observed to indicate abnormalities in drug distribution/disposition. It was hypothesized that the pharmacokinetic alteration after extreme dosing was because of induction of functional abnormalities in hepatopancreas. In addition, a single administration of OTC at 1000 mg/kg BW was anticipated to be a tolerated dose.
- 出版日期2011-8
