A COMPARATIVE STUDY OF THE PHOTOCHEMISTRY OF THE NON-STEROIDAL ANTI-INFLAMMATORY DRUGS, NAPROXEN, BENOXAPROFEN AND INDOMETHACIN

Abstract— The photochemical reactivity of the non-steroidal anti-inflammatory drugs, naproxen and indomethacin, has been studied and compared with benoxaprofen, a similar compound of known cutaneous phototoxicity. Although indomethacin shows some phosphorescence at 77 K, flash photolysis at room temperature revealed only a weak photoionization process, and no photochemical reactivity was detected in steady state photolysis. Naproxen has strong fluorescence and phosphorescence, and in laser flash photolysis showed photoionization and a triplet state species in approximately equal yield. Naproxen and benoxaprofen produced singlet oxygen with similar quantum yield, as deduced from the sensitized rates of photooxidation of 2,5-dimethylfuran. Naproxen underwent photodecarboxylation as detected by ESR-spin trap experiments with 2-methyl-2-nitrosopropane. The decarboxy-naproxen radical combined readily with oxygen in aerated solution, and l-(6-methoxy-2-napthyl)ethanol and 2-acetyl-6-methoxynaphthalene were formed as the oxidation products. In deaer-ated solution, the major product was 2-ethyI-6-methoxynaphthalene, with the alcohol also formed. In comparison, benoxaprofen also underwent decarboxylation, with much higher quantum yield, but the decarboxy-benoxaprofen radical did not add oxygen. This difference in photoreactivity between naproxen and benoxaprofen, together with the much lower molar absorptivity of naproxen are the significant factors in relating to the differences in reported levels of clinical photosensitivity responses.