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Title:   Author  item
                                            OLIVER, C - NORTH DAKOTA STATE UNIVitem
                                            CRAIGMILL, A - UC-DAVISitem
                                            CATON, J - NORTH DAKOTA STATE UNIVitem
                                            Anderson, Robinitem
                                            Smith, David
  Submitted to: Journal of Veterinary Pharmacology and Therapeutics
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/3/2007
                                    Publication  Date: 6/20/2007
                                    Citation: Oliver, C.E., Craigmill, A.L., Caton, J.S., Anderson, R.C., Smith, D.J. 2007.  Pharmacokinetics of ruminally-dosed sodium chlorate in beef cattle. Journal of Veterinary Pharmacology and Therapeutics 30:358-365.Interpretive Summary: An experimental chlorate product has been shown to reduce the number of human pathogenic bacteria such as E. coli O157:H7 and Salmonella enterica in gastrointestinal tracts of food animals, including cattle. Successful use of the experimental chlorate product in commercial feedlots depends upon variables such as dose, residues remaining in food tissues, and its efficacy in live animals. A major variable affecting efficacy of chlorate in live cattle is its efficient delivery to the lower gastrointestinal tract where it will have the most important impact at eliminating pathogens. Typically, delivery of an active substance to its site of action is influenced greatly by its absorption, metabolism, and excretion. This study was designed to determine the rate of chlorate absorption from the gastrointestinal tract and to determine the amount of chlorate delivered to the lower tract. In a previous study we determined that only a small fraction of an oral dose of chlorate is present in fecal and gastrointestinal material of cattle slaughtered 24 hours after their last exposure to chlorate. We learned in this study that it takes less than one hour for cattle to absorb greater than one-half of the dosed; thus one would expect little to no chlorate to reach the lower gastrointestinal tract by 24 hours after dosing.  This study highlights the need for a chlorate formulation that allows its delivery to the lower gastrointestinal tract of cattle.
                                Technical Abstract: The recently recognized potential of sodium chlorate as a possible pre-harvest food safety tool in meat animals has spurred interest in the pharmacokinetics of intraruminally-dosed chlorate. Six Loala cattle were assigned (one heifer and one steer per treatment) to one of three intraruminal doses of radiolabeled sodium [36Cl]chlorate (21, 42, or 63 mg/kg BW1) administered in four equal aliquots over a 24 h period. Blood and serum were collected (29 samples in 48 h). Total radioactive residues were measured and speciation of radioactivity was conducted. Chlorate appeared rapidly in blood and serum after dosing. Half-life of absorption was between 0.56 and 0.93 h, and serum chlorate concentrations peaked at 3.8 to 4.5 ppm in 3.5 h or less. Half-life of chlorate elimination was between 1.86 and 7.57 h depending on the dose and the pharmacokinetic model used. Absorption of chlorate removes it from its desired site of action, the lower gastrointestinal tract, thereby reducing its efficacy. Further research needs to be conducted to develop a chlorate formulation that will allow passage to the lower gastrointestinal tract.


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