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 chemical structures of the two regioisomers of BPD-MA are 9-methyl trans-(+/-)-18-ethenyl-4,4 alpha-dihydro-3,4- bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-4,4 alpha-dihydro-3,4- bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-23H,25H-benzo(b)porphine- 9,13-dipropanoate and 13-methyl-trans-(+/-)-18-ethenyl-4,4 alpha-dihydro-3,4- bis(methoxycarbonyl)-4 alpha, 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 phototoxicity was investigated in mice exposed to simulated sunlight (light) 3, 24, or 48 hr after receiving a single intravenous injection of vehicle or 2, 10, or 20 mg/kg of BPD-MA or Photofrin. The data were from two studies conducted using male and female CD1 mice (approximately 7 weeks old). The hair of the dorsal thoracic area was clipped 24 hr prior to exposure to light. Mice were exposed to light for 5 min. The clipped area of skin was the primary site for the evaluation of phototoxicity. Mice were observed for 2 weeks after treatment. There were no significant findings in controls or in mice given 2 mg/kg of BPD-MA. When mice were exposed to light 3 hr after dosing, both BPD-MA (10 or 20 mg/kg) and Photofrin (2, 10 or 20 mg/kg) caused phototoxicity. Death occurred in all mice given 20 mg/kg of BPD-MA or Photofrin, and in the majority of mice given 10 mg/kg of Photofrin.(ABSTRACT TRUNCATED AT 250 WORDS)