Development Of China Veterinary Drug Pharmacokinetics Database And The Tissue Depletion Of Oxytetracycline In Pig Edible Tissues

Veterinary drug has a great effect on the improvement of the quantity and quality of animal origin product. The use amount of the veterinary drug in food producing animals was raised quickly with the great development of animal husbandry in China. To the opposite of the development of animal husbandry, the veterinary drug industry was drop behind. Moreover, the unreasonable use of the veterinary drug in food producing animals causes serious problems on food safety issues and international trades. The pharmacokinetics studies the interaction between the animal body and the drug. The derived pharmacokinetics information was of great importance to the proper use of the drug and new drug development. The modern computer technology and information system gives us the feasibility to data storage and data sharing. Using database technology to collect and store the pharmacokinetics research information makes the research findings more systematic and formal. Developing a pharmacokinetics database could provide better service to the animal husbandry practice, research and education and also is of great importance for food safety and further development of the veterinary drug industrial.The wide use of oxytetracycline (OTC) long-acting injection in food-producing animals may lead to the residue of OTC in the edible tissues from treated animals that endanger consumer's health. The general method for drug residue monitor was to kill the animal and directly measure the residue in the edible tissue. However, the carcass will be discarded if the residue was greater than MRL, which would cause economic lost for the producers. The plasma could be used as surrogate matrix for monitoring the tissue residue if a correlation exits between tissue and plasma drug concentration. Meanwhile, the analysis method for plasma samples was more convenient and less time comsuming. For this regards, a residue depletion study was carried out to investigate the tissue depletion and plasma-tissue correlations of OTC in pigs. The tolerance limit predicted a plasma threshold concentration with 95% confidence that the tissue residue in 95% animal would less than MRL when OTC concentration in pig plasma less than this threshold concentration.1 The development of China veterinary drug pharmacokinetics databaseWe choose Windows Server 2003 as the operating system, IIS 6.0 as the application server, SQL Server 2000 as the background database, B/S three layers structure and ASP.NET technology to develop the veterinary pharmacokinetics database.880 biblio were extracted from 405 articles published from 1980s to the end of 2006. Developer and researcher could explore the pharmacokinetics or residual information on each chemical or target animal by specifying the chemical name or target animal name in pharmacokinetics database. This veterinary pharmacokinetics database provides a useful tool for manufacturer and researcher exploring pharmacokinetics information and facilitating to control the misuse and illegal use of veterinary drugs.2 The tissue depletion of oxytetracycline in swine edible tissueEighteen healthy crossbred pigs were treated with a long-acting OTC injection (TerramycinTM/LA) intramuscularly at a dose of 20 mg/kg body weight. Three pigs were sacrificed at 0.5,3,7,14,21 and 28 days post administration, respectively. Plasma, muscle, liver, kidney and injection site samples were collected. The oxytetracycline in swine tissue and plasma samples were extracted with McIlvaine buffer-EDTA buffer, cleaned and purified by a conditioned HLB SPE cartridge, eluted with methanol containing 10mM oxalic acid and redissolved. The chromatographic analysis was performed on Xterra(?) MS C8 column (Waters Corp.,250mm X 4.6mm) with the detector wavelength setting to 355 nm. The mobile phase was 0.01 M methanol-acetonitrile-oxalic acid (3:9:88, v/v/v). The limit of detection of instrument for oxytetracycline was 20μg/kg in swine muscle,25μg/kg in swine liver and kidney and 15μg/L in swine plasma. Recoveries of oxytetracycline determination method ranged from 80.2% to 87.6%, and intra-day coefficients of variation (CV) ranged from 1.2% to 7.4%. The analysis results showed that the highest concentrations were found in the injection site followed by the kidney, liver and muscle after administration. Significant high correlation of oxytetracycline concentration between plasma and edible tissues (muscle, liver, kidney, injection site) were found in the study. The linear correlation equation was y=0.8446x+0.6714 (r=0.9715) for muscle vs. plasma, y=0.8880x+1.1184 (r=0.9543) for liver vs. plasma, y=0.7132x+2.1101(r=0.9503) for kidney vs. plasma, y=1.8373x+2.9641(r=0.9880) for injection site vs. plasma, respectively. The tolerance limit procedure predicted with 95% confidence that plasma concentration less than 46μg/kg,60μg/kg,134μg/kg and 1μg/kg could ensure the OTC residue in 95% pig muscle, liver, kidney and injection do not exceed the corresponding MRLs, respectively.14,7,12 and 40 days were needed for oxytetracycline in swine plasma reaching the above concentrations, respectively. If a plasma concentration higher than these threshold concentrations were found in OTC residue monitor program, it is very likely that the drug residue in swine edible tissue exceeded the corresponding MRL.