Pharmacokinetics of a tri-glucoconjugated 5,10,15-(meta)-trihydroxyphenyl-20-phenyl porphyrin photosensitizer for PDT. A single dose study in the rat.
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.
Desroches
Marie-Catherine
MC
Laboratoire de Chimie Analytique UPRES EA 3343, Université Paris XI, Faculté de Pharmacie, 5 rue J-B. Clément, 92 296 Châtenay-Malabry, France.
Bautista-Sanchez
Antonia
A
Lamotte
Claire
C
Labeque
Bella
B
Auchère
Daniel
D
Farinotti
Robert
R
Maillard
Philippe
P
Grierson
David S
DS
Prognon
Patrice
P
Kasselouri
Athena
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
C515146:5,10,15-tri(3-O-glucosyloxyphenyl)-20-phenylporphyrin; D005960:Glucosides; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; C072269:temoporfin