Treatment and survival study in the C57BL/6J-APCMin/+(Min) mouse with R-flurbiprofen

WJ Wechter, ED Murray Jr, D Kantoci, DD Quiggle… - Life sciences, 2000 - Elsevier
WJ Wechter, ED Murray Jr, D Kantoci, DD Quiggle, DD Leipold, KM Gibson, JD McCracken
Life sciences, 2000Elsevier
Our previous studies with the mouse model of familial adenomatous polyposis (FAP),
C57BL/6J-APCMin/+ 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 (qod) schedule and compares it with sulindac sulfone. The
qod Schedule at 10 mg/kg was equally efficacious as qd treatment at the same dose. For the …
Our previous studies with the mouse model of familial adenomatous polyposis (FAP), C57BL/6J-APCMin/+ 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.
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