mTHPC

680.764

680.75

FU21S769PF

DTXSID7048619

C1669

L01XD05|L - Antineoplastic and immunomodulating agents

138

9.17

1.386±0.06 g/cm3(Predicted)

>250 °C

1.735

P261, P272, P280, P302+P352, P321, P333+P313, P363, P501

H317

Mice and rats experienced swelling and darkening of exposed tissue at single dosages of >0.85 mg/kg under normal lighting. Systemic toxicity presented as reduced red blood cell and platelet counts and increased white blood cell counts and liver and spleen weights. Skin inflammation, pycnotic spermatocytes and increased extramedullary haematopoiesis in spleen and the lymph nodes was also observed. Under low-light conditions mild phototoxicity was observed only at high doses. Severe phototoxicity has been seen in rats with repeated doses of up to 1 mg/kg/day under normal lighting. This effect is less severe under low-light conditions. Two weeks of repeated doses of 0.5-0.6 mg/kg/day resulted in inflammation of the injection site and skin in rats. At 0.3 mg/kg/day under low-light in rats, the only effect seen was an increase in white blood cell counts. In beagle dogs recieving repeated doses of up to 3mg/kg/day under low-light conditions, reddening of the skin and injection site inflammation was seen. Serious injection site damage was observed.

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.

For use in the treatment of patients with advanced squamous cell carcinoma of the head and neck failing standard therapies and who are unsuitable for radiotherapy, surgery, or systemic chemotherapy.|FDA Label|Foscan is indicated for the palliative treatment of patients with advanced head and neck squamous cell carcinoma failing prior therapies and unsuitable for radiotherapy, surgery or systemic chemotherapy.

Temoporfin is a photosensitizing agent. It enters cancer cells and is activated via light to produce reactive species which destroy the cell.

Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. (See all compounds classified as Photosensitizing Agents.)|Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells. (See all compounds classified as Radiation-Sensitizing Agents.)|Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

Tmax is 2-4 h after intravenous administration. Plasma concentration initially decreases rapidly then slowly rises to reach peak serum concentration.|Data on elimination in humans is limited. Animal data indicates Temoporfin is eliminated solely by the liver with two conjugated metabolites being excreted through bile. No enterohepatic recirculation has been observed with these metabolites.|The volume of distribution is 0.34-0.46 L/kg. Temoporfin is known to distribute into the tissues and preferentially collects in tumour tissue.|Temoporfin is cleared at a rate of 3.9-4.1 mL/h/kg.

The exact metabolic reactions Temoporfin undergoes are unknown. The drug metabolites have been identified as conjugates but specific information is unavailable.

Terminal plasma half life is 65 h. Elimination of Temoporfin is bi-exponential with the intial phase having a half-life of 30 h and a terminal half-life of 61-88 h.

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.

5,10,15,20-tetra(m-hydroxyphenyl)chlorin

Human drugs -> Foscan -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group