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-β- 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 5 h (20 h for m-THPC). The area under curve (AUC) and initial mean serum concentration ( C 0) 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.