NEW YORK (Reuters Health) - In people genotypically affected with familial adenomatous polyposis (FAP) who are taking sulindac to prevent clinical manifestations of the disease, prostaglandin levels in colorectal mucosa may be useful markers of effective drug levels.
In the February issue of Gastroenterology, a multicenter team led by Dr. Francis M. Giardiello of The Johns Hopkins University School of Medicine in Baltimore, Maryland, describes a study in which 41 subjects with family histories of familial adenomatous polyposis who had yet to develop adenomas were randomized to receive either sulindac or placebo for 48 months.
During colonoscopies performed to monitor for the development of polyps, the researchers took rectal mucosa biopsies in order to measure levels of 5 prostaglandins, as well as ornithine decarboxylase and polyamines. As they explain in their paper, they hoped to find that these compounds could help “to discriminate the development of neoplasia.”
According to the article, in the patients taking sulindac, levels of 4 of the 5 prostanoids were lower. Furthermore, levels of 3 prostaglandins -- prostaglandin D2, thromboxane B2, and 6-keto prostaglandin F1 alpha -- were significantly lower in the patients who were polyp free.
There were no significant differences in ornithine decarboxylase or polyamine levels either between study groups or between sulindac-treatment subjects with and without polyp development.
“Colorectal mucosal prostaglandin levels, but not ornithine decarboxylase or polyamines, may be valuable biomarkers to assess appropriate drug dosage and medication compliance in patients undergoing primary chemoprevention compliance with sulindac,” the authors conclude.
Source: Gastroenterology 2002;126:425-431. [ Google search on this article ]
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