MURINE PHARMACOKINETICS AND ANTITUMOR EFFICACY OF THE PHOTODYNAMIC SENSITIZER 2-[1-HEXYLOXYETHYL]-2-DEVINYL PYROPHEOPHORBIDE-A

The combination of the new photodynamic sensitizer 2-[1-hexyloxyethyl] -2-devinyl pyropheophorbide-a (HPPH) and laser light of wavelength 665 nm showed antitumor activity against two s.c.-implanted murine tumors . HPPH also sensitized normal mouse foot tissue to light but photosens itivity decreased rapidly with time after HPPH administration. Mechani stic studies revealed that HPPH induced little direct tumor cell toxic ity but was an effective mediator of vascular photodamage. Pharmacokin etic studies following intravenous injection of 1 mg [C-14]HPPH per ki logram revealed a biexponential decay with time, with plasma alpha and beta half-lives of 0.69 and 21 h respectively. Fecal excretion was th e primary route of elimination. The highest levels of [C-14]HPPH were found in the liver, which also showed the greatest long-term retention . The sequence of decreasing uptake levels was the liver, adrenals, lu ng, spleen, kidney, urinary bladder, heart, eye, skin, pancreas, muscl e, testes, fat and brain. This distribution correlated with the relati ve blood perfusion rates in the tissues.