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The cytotoxic and antitumor actions of Photofrin are light and oxygen dependent. Photodynamic Therapy (PDT) with Photofrin is a two-stage process. The first stage is the intravenous injection of Photofrin. Clearance from a variety of tissues occurs over 40-72 hours, but tumors, skin, and organs of the reticuloendothelial system (including liver and spleen) retain Photofrin for a longer period. Illumination with 630 nm wavelength laser light constitutes the second stage of therapy. Tumor selectivity in treatment occurs through a combination of selective retention of Photofrin and selective delivery of light. Cellular damage caused by Photofrin PDT is a consequence of the propagation of radical reactions. Radical initiation may occur after Photofrin absorbs light to form a porphyrin excited state. Spin transfer from Photofrin to molecular oxygen may then generate singlet oxygen. Subsequent radical reactions cans form superoxide and hydroxyl radicals. Tumor death also occurs through ischemic necrosis secondary to vascular occlusion that appears to be partly mediated by thromboxane A2 release. The laser treatment induces a photochemical, not a thermal, effect. The necrotic reaction and associated inflammatory responses may evolve over several days.
Following a 2mg/kg dose of porfimer sodium to 4 male cancer patients, the average peak plasma concentration was 15 +/- 3mcg/mL, the elimination half-life was 250 +/- 285 hours, the steady-state volume of distribution was 0.49 +/- 0.28L/kg, and the total plasma clearance was 0.051 +/- 0.035 mL/min/kg. The mean plasma concentration at 48 hours was 2.6 +/- 0.4 mcg/mL. The influence of impaired hepatic function on Photofrin disposition has not been evaluated.
Photofrin was approximately 90% protein bound in human serum, studied in vitro. The binding was independent of concentration over the concentration range of 20-100 mcg/mL.
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