Comparative Skin Phototoxicity in Mice with Two Photosensitizing Drugs: Benzoporphyrin Derivative Monoacid Ring A and Porfimer Sodium (Photofrin)

Benzoporphyrin derivative monoacid ring A (BPD-MA) and Photofrin(porfimer sodium) are photodynamic anticancer agents. The chemicalstructures of the two regioisomers of BPD-MA are 9-methyl trans-{±)-18-ethenyl-4,4-dihydro-3,4-bis(methoxycarbonyl)-4,8,14,19-tetramethyl-4,4-dihydro-3,4-bis (methoxycarbonyl)-4, 8,14,19-tetramethyl-23H, 25H-benzo(b)porphine-9,13-dipropanoateand 13-methyl-trans-(±)-18-ethenyl-4,4-dihydro-3,4-bis(methoxycarbonyl)-4,8,14,19-tetramethyl-23H,25H-benzo(b)porphine-9,13-dipropanoate.Photofrin (a registered trademark of American Cyanamid Co.)is a polyporphrin oligomer containing ester and ether linkages.The ability of BPD-MA or Photofrin to cause skin phototoxicitywas investigated in mice exposed to simulated sunlight (light)3, 24, or 48 hr after receiving a single intravenous injectionof vehicle or 2, 10, or 20 mg/kg of BPD-MA or Photofrin. Thedata were from two studies conducted using male and female CD1mice (7 weeks old). The hair of the dorsal thoracic area wasclipped 24 hr prior to exposure to light. Mice were exposedto light for 5 min. The clipped area of skin was the primarysite for the evaluation of phototoxicity. Mice were observedfor 2 weeks after treatment. There were no significant findingsin controls or in mice given 2 mg/kg of BPD-MA. When mice wereexposed to light 3 hr after dosing, both BPD-MA (10 or 20 mg/kg)and Photofrin (2, 10 or 20 mg/kg) caused phototoxicity. Deathoccurred in all mice given 20 mg/kg of BPD-MA or Photofrin,and in the majority of mice given 10 mg/kg of Photofrin. Insurviving mice, the skin of the back reacted by forming a largearea of eschar (scab). When mice were exposed to light 24 or48 hr after administration of BPD-MA or Photofrin, significantphototoxicity (browned skin and eschar formation) was observedonly in the mice given Photofrin. The data suggest that in miceBPD-MA causes substantial tissue injury when photoactivated3 hr after administration, but that the potential for phototoxicityis essentially gone after 24 hr. In contrast, phototoxicitywas elicited in the skin of mice exposed to simulated sunlight3, 24, and 48 hr after injection of Photofrin.