Aminolaevulinic acid-induced protoporphyrin IX pharmacokinetics in central and peripheral arteries of the rat.
Photodynamic therapy (PDT) based on the photosensitive protoporphyrin IX (PpIX) may prevent restenosis after transluminal angioplasty. PpIX is synthesized in mitochondria, which differ in number and activity among various tissues. Therefore, we questioned whether the course of PpIX concentration after systemic aminolaevulinic acid (ALA) administration differed among various arteries. ALA was administered intravenously (200 mg/kg) to male Wistar rats (n = 21). At varying time intervals (0, 1, 2, 3, 6, 12 and 24 h) both central and peripheral arteries were isolated and homogenized, and the concentration of the various heme intermediates was determined by a fluorometric extraction method. The maximal PpIX concentration was more than two-fold higher in peripheral arteries (20.49 +/- 3.0 to 24.0 +/- 7.5 pmol/mg protein) than in central arteries (0-9.46 +/- 0.01 pmol/mg protein) (P < 0.004). However, the amount of citrate synthase, reflecting the mitochondrial mass, was lower (0.14-0.61 and 1.87-2.32 U/mg protein, respectively). Apparently, the level of PpIX cannot simply be explained by the mitochondrial content of the arteries. The time interval of maximal PpIX accumulation was similar in peripheral and central arteries (2 h and 27 min vs. 2 h and 8 min) (P = 0.13). Thus, if the efficacy of PDT in vivo is directly related to the tissue concentration of PpIX, more effect can be expected in peripheral arteries than in central arteries.
Gabeler
Edward E E
EE
Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
Sluiter
Wim
W
van Hillegersberg
Richard
R
Edixhoven
Annie
A
Schoonderwoerd
Kees
K
Statius van Eps
Randolph G
RG
van Urk
Hero
H
D000622:Aminolevulinic Acid / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000737:chemistry; D011162:Porphobilinogen / Q000032:analysis / Q000097:blood; D011524:Protoporphyrins / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D011524:Protoporphyrins; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX