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.
Pervaiz
S
S
Baylor University Medical Center, Baylor Research Institute, Dallas, TX 75226.
Battaglino
M
M
Matthews
J L
JL
Gulliya
K S
KS
D000818:Animals; D004285:Dogs; D005260:Female; D006207:Half-Life; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D011744:Pyrimidinones / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D013552:Swine; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D011744:Pyrimidinones; C003954:merocyanine dye