Pharmacokinetics of a tri-glucoconjugated 5,10,15-(meta)-trihydroxyphenyl-20-phenyl porphyrin photosensitizer for PDT. A single dose study in the rat

J Photochem Photobiol B. 2006 Oct 2;85(1):56-64. doi: 10.1016/j.jphotobiol.2006.03.008. Epub 2006 Jun 12.

Abstract

Photodynamic therapy (PDT) involves a non invasive treatment of small and superficial cancers using a photosensitive drug and light to kill tumoral cells. 5,10,15-meso-tri-(meta-O-beta-D-glucosyloxyphenyl)-20-phenylporphyrin [m-TPP(glu)3] is a new photosensitizer (PS) with more enhanced photocytotoxicity relative to 5,10,15,20-meso-tetra-(meta-hydroxyphenyl) chlorin [m-THPC] (Foscan). It was injected intravenously once to healthy rats at three different doses (0.25, 0.5 and 1 mg kg(-1)) and compared to m-THPC (0.3 mg kg(-1)). Pharmacokinetic parameters for both photosensitizers were derived from plasma concentration-time data using a non-compartmental analysis and a two-compartment pharmacokinetic model. m-TPP(glu)3 is more rapidly eliminated throughout the organism than m-THPC. Its mean plasma clearance is 19 mL h(-1) kg(-1) (6 mL h(-1) kg(-1) for m-THPC), and its mean residence time is 5h (20 h for m-THPC). The area under curve (AUC) and initial mean serum concentration (C0) were found to be proportional to the dose. As for Foscan, no metabolite of m-TPP(glu)3 was detected in plasma. The biodistribution study demonstrates that the most significant amount of m-TPP(glu)3 was concentrated in organs such as lung, liver and spleen which are rich in reticulo-endothelial cells. Maximum concentrations were reached in organs 14 h after IV administration. At 48 h, the photosensitizer was essentially eliminated from all organs. Because of its shorter elimination time, m-TPP(glu)3 is more attractive than m-THPC as a PDT agent since secondary side effects of shorter duration could be expected.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Glucosides / administration & dosage
  • Glucosides / blood
  • Glucosides / pharmacokinetics*
  • Injections, Intravenous
  • Male
  • Mesoporphyrins / administration & dosage
  • Mesoporphyrins / pharmacokinetics
  • Mesoporphyrins / therapeutic use
  • Photochemotherapy*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / blood
  • Photosensitizing Agents / pharmacokinetics*
  • Porphyrins / administration & dosage
  • Porphyrins / blood
  • Porphyrins / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • 5,10,15-tri(3-O-glucosyloxyphenyl)-20-phenylporphyrin
  • Glucosides
  • Mesoporphyrins
  • Photosensitizing Agents
  • Porphyrins
  • temoporfin