sulindac and Ulcer

Our previous studies with the mouse model of familial adenomatous polyposis (FAP), C57BL/6J-APC(Min)/+ or Min mouse, demonstrated the optimal dose for adenoma reduction with R-flurbiprofen was 10 mg/kg/day as an undivided dose. Divided doses exhibited no increased efficaciousness. This study examines 10 mg/kg R-flurbiprofen daily (qd) on survival as well as a second daily (q.o.d.) schedule and compares it with sulindac sulfone. The q.o.d. schedule at 10 mg/kg was equally efficacious as qd treatment at the same dose. For the q.o.d. group, tumor number decreased similarly (p<0.01); while body weight gain (p<0.01), hematocrit and average tumor area (both, p<0.05) were improved compared with qd treatment. Treatment with R-flurbiprofen (10 mg/kg/day) increased survival significantly (p=0.0004, log-rank) compared to vehicle treated animals. Major biological endpoints (hematocrit, weight gain, tumor number, average and total area [99% reduction]) were significantly improved in treated animals (p<0.01). Sulindac sulfone treatment (50 mg/kg/day) of the Min mouse produced no significant biological benefit. The dose schedule study suggests that for tumor reduction it is necessary to attain a threshold drug-level but not necessarily sustain it over 24 hrs (pharmacodynamic t1/2 >> pharmacokinetic t1/2). During the period of administration R-flurbiprofen dramatically prolongs survival for the mouse model of the human disease, FAP.

Topics: Adenomatous Polyposis Coli; Alleles; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colon; Colonic Neoplasms; Cyclooxygenase Inhibitors; Female; Flurbiprofen; Mice; Mice, Inbred C57BL; Reverse Transcriptase Polymerase Chain Reaction; Sulindac; Survival Analysis; Ulcer

Topics: Adenomatous Polyposis Coli; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Middle Aged; Pouchitis; Sulindac; Ulcer

Topics: Administration, Oral; Adult; Esophageal Diseases; Humans; Male; Sulindac; Ulcer