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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

In vitro and in vivo binding of trimethoprim and sulphachlorpyridazine to equine food and digesta and their stability in caecal contents.

Binding of antibiotics to food has received little attention in equine medicine, although such binding could potentially reduce the bioavailability and clinical efficacy. In the present study, binding of trimethoprim (TMP) and sulphachlorpyridazine (SCP) to hay, grass silage and concentrate was investigated in vitro in buffer at pH 6.8 at different concentrations. The binding of TMP and SCP to caecal contents was also studied. In addition, the degradation of TMP and SCP by the caecal microflora was investigated by incubating sterilized and non-sterilized caecal contents for 3 h at 37 degrees C under anaerobic conditions and comparing the TMP and SCP contents. Further, a TMP/SCP powder formulation was adminstered orally with concentrate at a dose rate of 5 mg/kg TMP and 25 mg/kg SCP to three ponies with a caecum fistula; the animals were deprived of food for 8 h before administration. Blood samples, caecal contents samples and faecal samples were collected and analysed for TMP and SCP concentrations by means of high performance liquid chromatography (HPLC). Three non-fistulated ponies, acting as control animals, were fed the same dose of TMP/SCP with concentrate after 8 h of food deprivation and blood samples were taken. The percentage of in vitro binding of TMP as well as SCP to hay, grass silage and concentrate at concentrations of 4 micrograms/mL to 10 micrograms/mL was high (60-90%). TMP and SCP were also extensively bound to caecal contents (50-70%). At spiking concentrations above 10 micrograms/mL the percentage of binding decreased. There was no evidence of biodegradation of TMP or SCP in caecal contents. In vivo, both drugs could be detected in the caecal contents and in the faeces of three fistulated ponies. However, the fistulated ponies differed from the control ponies in that their TMP and SCP plasma concentrations were higher, and two fistulated ponies did not show double peaks in their plasma concentration-time curves. Therefore, the fistulated ponies did not provide an optimal model for in vivo binding studies. Despite this limitation, it can be concluded that binding of TMP and SCP to food is a major cause of the limited bioavailability of these drugs in the horse. It is hypothesized that the binding is reversible, and that a second absorption phase occurs in the large intestine, but part of the administered dose remains bound as both drugs were found in the faeces.[1]


  1. In vitro and in vivo binding of trimethoprim and sulphachlorpyridazine to equine food and digesta and their stability in caecal contents. Van Duijkeren, E., Kessels, B.G., Sloet van Oldruitenborgh-Oosterbaan, M.M., Breukink, H.J., Vulto, A.G., van Miert, A.S. J. Vet. Pharmacol. Ther. (1996) [Pubmed]
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