title: Aminolaevulinic acid-induced protoporphyrin IX pharmacokinetics in central and peripheral arteries of the rat.
abstract: 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.
authors.affiliation: Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Edward E E
authors.initials: EE
authors.lastname: Gabeler
authors.forename: Wim
authors.initials: W
authors.lastname: Sluiter
authors.forename: Richard
authors.initials: R
authors.lastname: van Hillegersberg
authors.forename: Annie
authors.initials: A
authors.lastname: Edixhoven
authors.forename: Kees
authors.initials: K
authors.lastname: Schoonderwoerd
authors.forename: Randolph G
authors.initials: RG
authors.lastname: Statius van Eps
authors.forename: Hero
authors.initials: H
authors.lastname: van Urk
mesh_terms: 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
chemical_list: D011524:Protoporphyrins; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX