Biodistribution and toxicity of photoproducts of merocyanine 540.

Light-activated merocyanine 540 (pMC540) has been shown in our earlier studies to be effective against certain types of tumor cells and viruses, including human immunodeficiency virus (HIV-1). To test the potential extracorporeal and systemic use of pMC540, its toxicity was investigated in DBA/2 mice, pigs, and dogs. The lethal dose in DBA/2 mice after an i.p. injection was 370 mg/kg, and the 50% lethal dose (LD50) was 320 mg/kg; however, following i.v. administration, the lethal dose and the LD50 dose were 240 and 160 mg/kg, respectively. Tritium-labeled MC540 was used to study the biodistribution of pMC540 in DBA/2 mice. Almost 70% of the injected radioactivity was excreted within 6 h of injection. After 1 week, the pMC540 was almost completely cleared, with only 1.89% of the activity remaining, and had a plasma half-life of 23 h. Pigs injected with an accumulated dose of 10 mg/kg and followed for a period of 30 days did not show adverse signs of toxicity as monitored by SMAC-28 analysis, CBC profile, and blood-coagulation studies. A dog injected with a single dose of 20 mg/kg showed induction of the hepatic enzymes glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (AST); however, serum levels of gamma-glutamyl transpeptidase (GGT) remained unchanged. The data presented herein may serve to identify certain drug-dose limitations in the systemic use of pMC540.
AuthorsS Pervaiz, M Battaglino, J L Matthews, K S Gulliya
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 31 Issue 6 Pg. 467-74 ( 1993) ISSN: 0344-5704 [Print] GERMANY
PMID8453686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Photosensitizing Agents
  • Pyrimidinones
  • merocyanine dye
  • Animals
  • Dogs
  • Female
  • Half-Life
  • Male
  • Mice
  • Mice, Inbred DBA
  • Photochemistry
  • Photosensitizing Agents (chemistry, pharmacokinetics, toxicity)
  • Pyrimidinones (chemistry, pharmacokinetics, toxicity)
  • Swine
  • Tissue Distribution

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