Effect of administration route and estrogen manipulation on endometrial uptake of Photofrin porfimer sodium.

Abstract

Our purpose was to evaluate the influence of the route of drug administration and target tissue vascularity on the distribution of a photosensitizer, Photofrin porfimer sodium, in the uterus. The study was divided in two phases. In phase I 80 mature female rats were hormonally suppressed and then stimulated with estrogen. They were randomized to receive intravenous, intraperitoneal, or intrauterine Photofrin and killed 3, 6, 24, or 48 hours later. Drug distribution and levels were then determined. In phase II 40 female rats were randomized to receive hormonal stimulation, suppression, both, or neither. All received intrauterine Photofrin and were killed 24 hours later. Statistical analysis was performed with the unpaired t test and the two-way analysis of variance. Intrauterine administration was determined to be the simplest and most effective method of delivery because it provided for optimal uptake and distribution (p = 0.05) within the uterus, at lower doses. Selective localization of photosensitizer within the target tissue suggests that highly selective photodynamic destruction of endometrial tissue can be achieved. Furthermore, the combination of intrauterine administration of photosensitizer with estrogen adjuvant may minimize the most debilitating side effect of Photofrin, cutaneous phototoxicity.