DISTRIBUTION AND ELIMINATION OF PHOTOFRIN II IN MICE

The distribution and elimination of [₁₄C]PH, the radioisotopically‐labeled equivalent of the mixture of porphyrins known as Photofrin II used in the photodynamic treatment of solid tumors, were determined in tumor‐free and SMT‐F tumor‐bearing DBA/2 Ha‐DD mice. Following i.p. injection, drug was absorbed from the peritoneum with a half‐life of about 1 h; elimination from plasma was rapid, declining about 1.4 logs in concentration over 48 h following i.v. administration. However, some [₁₄C]‐activity was still detectable after 75 days. Normal tissues take up the drug within about 7.5 h after administration, with peak concentrations distributed as follows: liver, adrenal gland, urinary bladder > pancreas, kidney, spleen > stomach, bone, lung, heart > muscle > brain. Only skeletal muscle, brain, and skin located contralaterally to subcutaneously implanted SMT‐F tumors had peak [₁₄C]‐activities lower than tumor tissue; skin overlying SMT‐F tumors showed concentrations not significantly different (P > 0.3) from tumor. After 75 days all tissues examined retained some fraction of [₁₄C]‐activity, ranging from 16% for kidney to 61% for spleen, of the initial peak tissue levels. The primary route of elimination of Photofrin II was through the bile‐gut pathway, with greater than 59% of the administered [₁₄C]‐activity recovered in the feces, and only about 6% in the urine, over 192 h. HPLC analyses of fecal extracts showed that mostly monomeric and other low molecular weight porphyrin components of Photofrin II were eliminated. The higher molecular weight oligomeric fractions of Photofrin II were retained in liver and spleen up to 14 days after injection.