Dược Lực Học :
Patients with UC have reduced AP levels and activity in the inflamed tissue in the intestines. A short treatment with AP helps to restore the intestinal mucosal barrier in UC patients, which can be classified as a disease modifying antiinflammatory effect.
Cơ Chế Tác Dụng :
Alkaline Phosphatase (AP) is an oral treatment and has a very
favorable side-effect profile. AP only acts locally in the colon to reduce the continuous inflammation of the colon by endotoxin from Gram-negative bacteria and extracellular ATP in UC patients.
Two substrates that can disturb the homeostasis in
human organs are endotoxin from Gram-negative bacteria (LPS) and adenosine triphosphate (ATP). Dephosphorylation of LPS and extracellular ATP by AP has been shown to result in restoration of homeostasis in the target organs such as GI tract and kidney, through reduction of inflammationinduced
damage. In the gastrointestinal tract, the prime source of LPS is derived from the residing Gram-negative microorganisms. In UC patients the mucosal surface of the colon wall is characterized by intermittent lesions and hyperpermeability caused by chronic inflammation. A consequence of the damaged intestinal mucosa is a reduced AP level and an increased influx of LPS responsive cells that
maintain the inflammatory response. In the gastrointestinal tract, the prime source of LPS is derived from the residing Gram-negative microorganisms. AP reduces LPS-mediated
inflammation, by preventing activation of the intestinal epithelium and preventing systemic inflammatory responses that result from transmigration of endotoxin though the
leaky inflamed intestinal mucosa.
Chỉ Định :
Investigated for use/treatment in ulcerative colitis.