TOPICAL APPLICATION OF WR-2721 ACHIEVES HIGH-CONCENTRATIONS IN THE RECTAL WALL

Rectal wall injury is an important treatment-related morbidity in pati ents treated with radiation for prostate cancer, We have undertaken th is study to investigate the merits of topical intrarectal application of the radioprotective compound WR-2721. Male Copenhagen rats were inj ected intrarectally with 2% WR-2721 gel, At 10, 20, 30 and 40 min afte r application, a laparotomy was performed, and the rectum and prostate were removed. Concentrations of total WR-1065 (the active metabolite of WR-2721) were determined in these samples by an HPLC assay. While t he concentration in the rectal wall tended to increase with time, it d id not change substantially in the prostate. The concentration in the rectal wall was found to be significantly higher at all times, We conc lude that preferential accumulation of WR-2721 in the rectal wall can be achieved by topical application, This is a promising approach to mo difying rectal wall tolerance that deserves more study. (C) 1995 by Ra diation Research Society