Ten 3-month-old pigs were treated with feed containing 300 mg furazolidone per kg for a period of 7 days, followed by withdrawal periods of 0, 1, 2, 3 or 4 weeks (two per group). The treatment resulted in the formation of protein-bound metabolites containing an intact 3-amino-2-oxazolidinone (AOZ) side-chain that could be chemically released and then detected in liver, kidney and rump muscle tissues even 4 weeks after dosing. In tissues from animals killed at the end of the medication period, 993, 600 and 124 ng of AOZ were released from 1 g of liver, kidney and muscle respectively. In the tissues of the animals killed after a further 4 weeks the corresponding levels were 41, 7 and 10 ng/g respectively. It may be concluded that long withdrawal periods prior to slaughter for human consumption are required for pigs treated with furazolidone, because of the long residence time of protein-bound AOZ and the possibility that it might be released from its protein-bound form in the stomach and subsequently be transformed into a hydrazine.
1. A sensitive method for the determination of 3-(4-cyano-2-oxobutylidene amino)-2-oxazolidone, the open-chain cyano-derivative of the veterinary drug furazolidone, in swine plasma and tissues is described. 2. After dosing adult swine orally with furazolidone (690 mg/animal per day) for 10 days no furazolidone was detected in liver, kidney and muscle (less than 2 ng/g). The half life of furazolidone as measured from the terminal phase of the plasma curves was 45 minutes. In urine, small amounts (less than 0.3% of total dose) of furazolidone were detected. 3. In contrast to other animals, 3-(4-cyano-2-oxobutylidene amino)-2-oxazolidone is a minor metabolite in swine with a plasma half life of 4 h. No cyano-derivative was detected in liver and kidney (less than 5 ng/g) 2 h after the last administration of furazolidone; 24 h after the last administration, the concentration in plasma was less than 2 ng/ml and in muscle less than 5/g. 4. The cyano-derivative was not mutagenic in the Salmonella/microsome test, with or without metabolic activation.
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