Marguery M C, Chouini-Lalanne N, Ader J C, Paillous N
Laboratoire des I.M.R.C.P., UMR CNRS, Université Paul Sabatier, Toulouse, France.
Photochem Photobiol. 1998 Nov;68(5):679-84.
Fenofibrate and ketoprofen (KP) are two drugs of similar structure derived from that of benzophenone. Both are photoallergic and promote cross reactions in patients. However, the cutaneous photosensitizing properties of KP also include phototoxic effects and are more frequently mentioned. To account for this difference in their in vivo properties, their in vitro photosensitizing properties on DNA were compared. First, it was shown that under irradiation at 313 nm, fenofibric acid (FB), the main metabolite of fenofibrate, photosensitized DNA cleavage by a radical mechanism similar to that proposed for KP but with a 50 times lower efficiency. Furthermore, FB did not photosensitize the formation of pyrimidine dimers into DNA in contrast to KP, which did promote this type of DNA damage. Their difference in efficiency as DNA breakers was compared to their relative photochemical reactivity and the quantum yield of FB photolysis was found to be eightfold lower than that of KP. The reactivity of these drugs cannot explain alone the difference in their photosensitizing properties. Other factors such as the magnitude of the ionic character of the photodecarboxylation pathway of these benzophenone-like drugs are considered in the discussion.
非诺贝特和酮洛芬（KP）是两种结构与二苯甲酮相似的药物。二者均具有光过敏性，并会在患者体内引发交叉反应。然而，KP的皮肤光敏特性还包括光毒性作用，且更常被提及。为解释它们体内特性的这种差异，对二者在体外对DNA的光敏特性进行了比较。首先，研究表明，在313nm光照下，非诺贝特的主要代谢产物非诺贝特酸（FB）通过与KP类似的自由基机制使DNA发生光致敏裂解，但效率低50倍。此外，与KP不同，FB不会使嘧啶二聚体在DNA中形成，而KP确实会引发此类DNA损伤。将它们作为DNA断裂剂的效率差异与其相对光化学反应性进行了比较，发现FB的光解量子产率比KP低八倍。这些药物的反应性本身无法解释它们光敏特性的差异。讨论中考虑了其他因素，如这些二苯甲酮类药物光脱羧途径的离子特性大小。
