Effect of orlistat on fecal fat, fecal biliary acids, and colonic cell proliferation in obese subjects.
OBJECTIVE
Orlistat is a weight management agent that selectively inhibits gastrointestinal lipase activity. Because of orlistat's mode of action, increased fecal fat is presented to the colonic mucosa, and fecal bile acid and free fatty acid composition may be altered during treatment. Our aim was to assess the effect of treatment of obese subjects with orlistat 120 mg 3 times a day for 6 weeks on fecal lipid and bile acid parameters and colonic mucosal cell proliferation.


METHODS
Twenty-four obese (body mass index, 30-40 kg/m2) but otherwise healthy male and female subjects were enrolled in a single-center, randomized, double-blind, placebo-controlled, parallel-group study. Participants were hospitalized during days 1-3 and 33-42 of treatment and were treated as outpatients for the remaining days.


RESULTS
Treatment with orlistat for 6 weeks resulted in significantly greater increases in fecal weight, total fecal fat, and fecal free fatty acids than placebo. Total fecal bile acid amounts decreased slightly with orlistat, and increased significantly with placebo treatment (P < .05 between-group difference). Orlistat did not alter colonic cell proliferation as assessed by the 3 proliferative indices (5-bromo-2-deoxyuridine, whole crypt mitotic count, and proliferating cell nuclear antigen).


CONCLUSIONS
Biochemical changes in fecal composition related to the pharmacodynamic mode of action of orlistat are not accompanied by altered colonic cell proliferation, a putative biomarker of colon cancer risk.
Ahnen
Dennis J
DJ
University of Colorado Health Sciences Center and Department of Veterans Affairs Medical Center, Denver, Colorado 80220, USA. dennis.ahnen@uchsc.edu
Guerciolini
Roberto
R
Hauptman
Jonathan
J
Blotner
Steven
S
Woods
Cindy J
CJ
Wargovich
Michael J
MJ
D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism*; D001706:Biopsy; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000378:metabolism*; D004311:Double-Blind Method; D005227:Fatty Acids / Q000378:metabolism*; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D000077403:Orlistat; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D019440:Anti-Obesity Agents; D001647:Bile Acids and Salts; D004041:Dietary Fats; D005227:Fatty Acids; D007783:Lactones; D018809:Proliferating Cell Nuclear Antigen; D000077403:Orlistat; D001973:Bromodeoxyuridine