Temoporfin

Temoporfin is 85-88% bound to plasma proteins. Temoporfin initially binds and aggregates to an unknown high density protein. This makes up about 70% of the bound drug immediately after administration. The remainder is bound to plasma lipoproteins with 22% bound to high density lipoprotein (HDL), 4% bound to low density lipoprotein (LDL), and 4% bound to very low density lipoprotein (VLDL). Within 24 hours after administration, Temoporfin undergoes redistribution to lipoproteins with about 73% bound to HDL, 8% bound to LDL, and 3% bound to VLDL. Only 17% remains bound to the unknown high density protein after redistribution.

Temoporfin is excited from ground state to the first excited singlet state by the application of 652 nm light. It is then thought to undergo intersystem crossing to an excited triplet state which is longer lived and able to interact with surrounding molecules. It is then thought to produce cytotoxic species by either a Type I or Type II reaction typical of agents used in photodynamic therapy. Type I involves either hydrogen abstraction of electron transfer from the excited photosensitizer to a substrate molecule to produce free radicals or radical ions. Type II reactions involve a similar reaction with oxygen as the substrate to produce reactive oxygen species. These reactive products cause oxidative damage to the cancer cell resulting in cell death. There is evidence that photodynamic therapy with Temoporfin activates macrophages and increases phagocytosis. These activated macrophages also produce more tumour necrosis factor-α (TNF-α) and nitric oxide (NO). It is thought that this increase in macrophage activity contributes to the efficacy of therapy through phagocytosis of cancer cells and increased cell death signalling though TNF-α. The increase in NO production likely contributes to oxidative damage through reactive nitrogen species.