Murine pharmacokinetics and antitumor efficacy of the photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a.
The combination of the new photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) and laser light of wavelength 665 nm showed antitumor activity against two s.c.-implanted murine tumors. HPPH also sensitized normal mouse foot tissue to light but photosensitivity decreased rapidly with time after HPPH administration. Mechanistic studies revealed that HPPH induced little direct tumor cell toxicity but was an effective mediator of vascular photodamage. Pharmacokinetic studies following intravenous injection of 1 mg [14C]HPPH per kilogram revealed a biexponential decay with time, with plasma alpha and beta half-lives of 0.69 and 21 h respectively. Fecal excretion was the primary route of elimination. The highest levels of [14C]HPPH were found in the liver, which also showed the greatest long-term retention. The sequence of decreasing uptake levels was the liver, adrenals, lung, spleen, kidney, urinary bladder, heart, eye, skin, pancreas, muscle, testes, fat and brain. This distribution correlated with the relative blood perfusion rates in the tissues.
Bellnier
D A
DA
Division of Radiation Biology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Henderson
B W
BW
Pandey
R K
RK
Potter
W R
WR
Dougherty
T J
TJ
D000818:Animals; D001693:Biological Transport, Active; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a