Giuffrida S, De Guidi G, Sortino S, Chillemi R, Costanzo L L, Condorelli G
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
J Photochem Photobiol B. 1995 Aug;29(2-3):125-33. doi: 10.1016/1011-1344(95)07133-m.
The photosensitizing properties of tolmetin, 5-(p-toluoyl)-1-methyl-2-pyrrolyacetic acid (TLM), have been studied in vitro following the lysis of erythrocytes in phosphate buffer suspensions irradiated with UVA light in the presence of the drug. It was found that the phototoxic properties of the drug are negligible in nitrogen and significant in aerated medium, but that they decrease in oxygen-saturated solution. The investigation of the drug photolysis showed that TLM undergoes photodecarboxylation to p-tolyl 1,2-dimethyl-5-pyrrolyl ketone in nitrogen and to p-tolyl 1-methyl-2-hydroxymethyl-5-pyrrolyl ketone and 5-(p-toluoyl)-1-methyl-2-pyrrole carbaldehyde in air. These photoproducts also undergo photodegradation. The comparison between the photohaemolysis and photolysis results and the effect of suitable additives such as sodium azide, mannitol, butylated hydroxy-anisole, reduced glutathione, superoxide dismutase and copper (II) suggest that the phototoxicity of TLM can be attributed essentially to singlet oxygen in the first step and to its photoproducts when they accumulate and compete with the starting drug in light absorption. Their phototoxic effect is much higher with respect to that of TLM, as shown by comparison of the doses needed to attain 50% photohaemolysis.
在药物存在的情况下，用紫外线A（UVA）照射磷酸盐缓冲液悬浮液中的红细胞使其裂解后，已在体外研究了托美丁（5-(对甲苯甲酰基)-1-甲基-2-吡咯乙酸，TLM）的光敏特性。结果发现，该药物在氮气中的光毒性可忽略不计，在通气介质中有显著光毒性，但在氧饱和溶液中光毒性会降低。对该药物光解的研究表明，TLM在氮气中发生光脱羧反应生成对甲苯基1,2-二甲基-5-吡咯基酮，在空气中生成对甲苯基1-甲基-2-羟甲基-5-吡咯基酮和5-(对甲苯甲酰基)-1-甲基-2-吡咯甲醛。这些光产物也会发生光降解。光溶血和光解结果之间的比较以及叠氮化钠、甘露醇、丁基化羟基茴香醚、还原型谷胱甘肽、超氧化物歧化酶和铜（II）等合适添加剂的作用表明，TLM的光毒性在第一步主要可归因于单线态氧，当其光产物积累并在光吸收方面与起始药物竞争时，光毒性则归因于这些光产物。通过比较达到50%光溶血所需的剂量可以看出，它们的光毒性作用相对于TLM要高得多。
