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             PHARMACOLOGICAL ACTIVITIES - TOXICOLOGY - DRUG INTERACTIONS





                               Probiotics

                               Food and Agriculture Organization of the United Nations (FAO) and World Health Organization
                               (WHO)  define  probiotics  as:  “Live  microorganisms  which  when  administered  in  adequate
                               amounts confer a health benefit on the host”. Maintenance of the bacterial flora and antagonism of
                               pathogenic bacteria in the gastrointestinal tract are important defence mechanisms by preventing
                               colonization of pathogenic bacteria. The bacterial flora achieves this by:

                               •  Preventing adherence of the pathogens to mucosal cells by occupying the site or by stearic
                                 hindrance (Reed et al., 2004).
                               •  Production of volatile fatty acids by normal microbial digestive processes to create an environment that is toxic to many bacterial
                                 populations, particularly the Enterobacteriaceae (Reed et al., 2004).
                               •  Production of antibacterial factors that allow symbiosis rather than competition (Reed et al., 2004).

                               Probiotics are capable of colonizing the alimentary tract in dogs and as a result these beneficial
                               bacteria take an important part in the treatment of many diseases including chronic inflammatory
                               bowel disease [IBD] (Chrzastowska et al., 2009). A study has demonstrated that modulation of
                               bacterial flora by increasing bifidobacteria and dietary intervention may be beneficial to cats with
                               IBD (Inness et al., 2007). In a randomised, double blind and single centre study of dogs with acute
                               diarrhoea and vomiting, treatment with probiotics reduced the convalescence time (Herstad et al.,
                               2010). A study on the resolution rate of acute idiopathic diarrhoea in dogs, nutritional management
                               with the probiotic reduced the time to resolution (Kelley et al., 2009). Probiotic supplementation
                               has been found to enhance specific immune functions at both the mucosal and systemic levels in
                               puppies (Chung et al., 2009). Lactobacillus acidophilus can also stabilize the digestive processes
                               in dogs with non-specific dietary sensitivity (Pascher et al., 2008).




                 Toxicity for probiotics has not been documented in dogs and cats when administered orally in therapeutic doses.
                 Oral LD  for three lactobacilli strains was >50 g/kg of body weight (1011 Colony Forming Units) in mice.
                        50
                 Other reports include LD  >50g/kg of body weight for Bifidobacterium longum, LD  >6 g/kg of body weight
                                      50
                                                                                       50
            TOXICOLOGY  2010).                  50
                 for Lactobacillus rhamnosus, and LD  >5 g/kg of body weight for Lactobacillus salivarius (Watson & Preedy,

                 Equivalent toxic dose in 20 kg dog:   >1000 g PO of Bifidobacterium longum; >120 g PO of Lactobacillus
                                                rhamnosus;  >100 g PO of Lactobacillus salivarius.
                 Equivalent toxic dose in 5 kg cat:    >250 g PO of Bifidobacterium longum; >30 g PO of Lactobacillus
                                                rhamnosus;  >25 g PO of Lactobacillus salivarius.



                   DRUG     Validated interactions studies do not exist for probiotic preparations. Clinical interactions with
          INTERACTIONS     other drugs have not been reported.










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