Antimicrobial agents are essential for controlling bacterial disease in food-producing animals and contribute to the stable production of safe animal products. The use of antimicrobial agents in these animals affects the emergence and prevalence of antimicrobial resistance in bacteria isolated from animals and animal products. As disease-causing bacteria are often transferred from food-producing animals to humans, the food chain is considered a route of transmission for the resistant bacteria and/or resistance genes. The Food Safety Commission of Japan (FSC) has been assessing the risk posed to human health by the transmission of antimicrobial-resistant bacteria from livestock products via the food chain. In addition to the FSC's risk assessments, the Japanese Ministry of Agriculture, Forestry and Fisheries has developed risk-management guidelines to determine feasible risk-management options for the use of antimicrobial veterinary medicinal products during farming practices. This report includes information on risk assessment and novel approaches for risk management of antimicrobial veterinary medicinal products for mitigating the risk of development and prevalence of antimicrobial resistance in bacteria originating from food-producing animals in Japan.
SUMMARYAfter intravenous (1 mg/kg body weight), intramuscular (1 mg/kg body weight) and oral (1 and 50 mg/kg body weight) administration of folic acid (FA) to pigs, plasma levels of FA, tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5MF) were determined by using highperformance liquid chromatography. The pharmacokinetic profile of plasma FA after oral administration indicated an absorption rate-limited elimination, i.e., so called 'flip-flop' phenomenon. The bioavailability of FA was quite low after a high oral dose (F=0.01), in contrast to a high value after intramuscular administration (F=0.95). The plasma levels of biologically active, reduced forms of folates (THF and 5MF) were significantly increased over their basal levels after IV and IM administration to FA. The levels of these active folates were not increased after oral administration of a similair dose of FA. A 50 times higher dose was required to increase the active folates to the levels observed after IV and IM administration.
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