With large salicylate doses, the kinetics switch from first-order to zero-order, as metabolic pathways become saturated and renal excretion becomes increasingly important.Salicylates are excreted mainly by the kidneys as salicyluric acid (75%), free salicylic acid (10%), salicylic phenol (10%), and acyl glucuronides (5%), gentisic acid (< 1%), and 2,3-dihydroxybenzoic acid. When small doses (less than 250 mg in an adult) are ingested, all pathways proceed by first-order kinetics, with an elimination half-life of about 2.0 h to 4.5 h. When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15 h to 30 h), because the biotransformation pathways concerned with the formation of salicyluric acid and salicyl phenolic glucuronide become saturated. Renal excretion of salicylic acid becomes increasingly important as the metabolic pathways become saturated, because it is extremely sensitive to changes in urinary pH. A 10- to 20-fold increase in renal clearance occurs when urine pH is increased from 5 to 8. The use of urinary alkalinization exploits this particular aspect of salicylate elimination. It was found that short-term aspirin use in therapeutic doses might precipitate reversible acute kidney injury when the patient was ill with glomerulonephritis or cirrhosis. Aspirin for some patients with chronic kidney disease and some children with congestive heart failure was contraindicated. History
Medicines made from willow and other salicylate-rich plants appear in clay tablets from ancient Sumer as well as the Ebers Papyrus from ancient Egypt.
This can be a limiting factor in the use of maintenance metronidazole to suppress chronic pouchitis.Other therapies which have been shown to be effective include probiotics for pouchitis, the application of which usually begins as soon as any antibiotic course is completed so as to re-populate the pouch with beneficial bacteria. The most clinically researched multi-strain probiotic for pouchitis is the De Simone Formulation (formulation name) invented by medical doctor Professor Claudio De Simone. It is currently sold under a variety of brand names globally including Visbiome in the U.S. and Canada, Vivomixx in Europe, and Innovall CU in Germany.Biologics, such as anti-tumor necrosis factor antibodies, may also be useful but the evidence for their use is largely anecdotal. Research
A pilot study on the effect of reducing dietary FODMAP intake on bowel function in people without a colon indicates there might be a relation between pouchitis and FODMAP diets.Alicaforsen (an antisense inhibitor which targets the messenger RNA for the production of human ICAM-1 protein) was evaluated in a Phase 3 clinical trial, which did not meet the co-primary endpoints in the primary analysis (an adaptation of the Mayo Score of improvement in endoscopic remission and bowel frequency). References


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