Temoporfin

Temoporfin is a photosensitising agent used in the photodynamic therapy of tumours.

The pharmacological activity is initiated by photoactivation of temoporfin with non-thermal light at 652 nm following intravenous administration. The therapeutic effect is mediated through the generation of highly reactive oxygen species, a process dependent on the intracellular interaction of temoporfin with light and oxygen.

Temoporfin is a low clearance substance with a terminal plasma half-life of 65 hours in patients. Peak plasma levels occur at 2-4 hours post-injection thereafter plasma levels decline in a bi-exponential manner. An extensive volume of distribution is observed that is intermediate between total and extracellular body water. Temoporfin does not concentrate in the tissues. Plasma protein binding is at 85-87%. Temoporfin is bound to plasma lipoproteins and high density proteins such as albumin in the blood. By 15 days post-infusion, temoporfin plasma concentration has declined to background such that patients are generally able to begin a gradual return to normal outdoor lighting conditions.

Limited data are available on the elimination of temoporfin in humans. Animal data show temoporfin is exclusively eliminated by the liver into the bile and excreted in the faeces. Two major metabolites of temoporfin are eliminated into the bile. There is no enterohepatic recirculation of these metabolites. Both these metabolites show conjugated character. No metabolites are seen in the systemic circulation.

In repeated dose toxicity studies in rats and dogs, the main undesirable effects of temoporfin were phototoxicity and adverse injection site reactions. Local irritancy of temoporfin solution for injection after intravenous administration occurred with all doses. High rates of administration caused death in dogs and rabbits. No other signs of toxicity were found, however, in dogs treated with the recommended therapeutic dose, systemic exposure exceeded that of humans.

The genotoxicity of temoporfin has been investigated to a limited extent. Due to the generation of reactive oxygen species, temoporfin poses a minor risk of mutagenicity. This risk can be controlled in the clinical situation by minimising direct exposure to light.

In developmental toxicity studies in rabbits, temoporfin, at systemic exposures equal to those obtained in humans with the recommended therapeutic dose, caused an increase in early post-implantation loss. Although no other developmental effects were observed, the applied doses were not sufficiently in excess of the human therapeutic dose to provide an adequate margin of safety.