RAT REPRODUCTIVE-PERFORMANCE FOLLOWING PHOTODYNAMIC THERAPY WITH TOPICALLY ADMINISTERED PHOTOFRIN

A rat animal model was used for comparing the photodynamic efficacy of two formulations of topically administered Photofrin in the uterus: 0 .7 mg/kg Photofrin and 0.7 mg/kg Photofrin + 4% Atone, a penetration-e nhancing agent, Uterine structure and reproductive performance were ev aluated following illumination with 80 J/cm(2) of 630 mn light, Fluore scence microscopy was employed to determine drug localization in froze n uterine sections at various times after drug administration, Functio nality studies demonstrated a significant reduction in the number of i mplantations per treated uterine horn compared to controls, The mean n umber of implantations decreased systematically on increasing the inte rval between Photofrin administration and light application, At 72 h, 0.88 +/- 0.52 gestational sacs per rat were recorded with Photofrin th erapy, compared with 8.1 +/- 1.12 (P = 0.01) on the untreated side, in dicating nearly complete loss of reproductive capability. Similar resu lts were achieved after only 3 h treatment with Photofrin+Azone (0.38 +/- 0.26 sacs per rat versus 7.5 +/- 1.07 on the untreated side; P = 0 .01), This indicates that the effect of Photofrin can be enhanced eith er by extending the drug incubation period from 3 to 72 h or by adding the penetration-enhancing drug Atone, Fluorescence pharmacokinetic st udies suggest that both forms of topically administered Photofrin are diffusely distributed throughout the endometrium at virtually the same rate, However, Atone may enhance the selectivity of photodynamic ther apy by facilitating drug targeting to critical endometrial structures.