Cosserat-Gerardin I, Bezdetnaya L, Notter D, Vigneron C, Guillemin F
Laboratoire d' Hématologie, Physiologie et Biologie Cellulaire, Faculté de Pharmacie, Nancy, France.
J Photochem Photobiol B. 2000 Dec;59(1-3):72-9. doi: 10.1016/s1011-1344(00)00142-1.
Hexylester of 5-aminolevulinic acid (hALA) has been considered as an alternative to 5-aminolevulinic acid (ALA) for the treatment of malignancies of different origin. The present study addresses the ALA and hALA-induced PpIX pharmacokinetic profile using rat bladder carcinoma cells (AY27). The total PpIX content measured spectrofluorimetrically after extraction procedure at the end of 2 h incubation was at least 1.5-fold greater with hALA compared to ALA despite the difference in concentration of several orders between the two compounds (1 or 5 mM ALA and 5 or 10 x 10(-3) mM hALA). Considerable PpIX efflux was detected in the extracellular medium at the end of the incubation. With 5 mM ALA and 10 x 10(-3) mM hALA, PpIX build-up was continued beyond the incubation period pointing out to enzyme saturation in the biosynthetic pathway or/and the constitution of ALA reserve. Red laser light (lambda=630 nm) irradiation of AY27 cells after 2 h incubation with increasing ALA or hALA concentrations resulted in a nearly equal photocytotoxicity.
5-氨基乙酰丙酸己酯（hALA）被认为是5-氨基乙酰丙酸（ALA）的替代物，可用于治疗不同起源的恶性肿瘤。本研究使用大鼠膀胱癌细胞（AY27）研究了ALA和hALA诱导的原卟啉IX（PpIX）的药代动力学特征。尽管两种化合物的浓度相差几个数量级（1或5 mM ALA和5或10×10⁻³ mM hALA），但在孵育2小时结束时，通过分光荧光法测定的总PpIX含量，hALA比ALA至少高1.5倍。孵育结束时，在细胞外培养基中检测到大量的PpIX流出。使用5 mM ALA和10×10⁻³ mM hALA时，孵育期过后PpIX仍持续积累，这表明生物合成途径中的酶饱和或/和ALA储备的形成。在分别用递增浓度的ALA或hALA孵育2小时后，用红色激光（λ = 630 nm）照射AY27细胞，结果显示光细胞毒性几乎相等。
