Ketoprofen: experimental overview of dermal toxicity

Ketoprofen (KP) is a widely used non-steroidal anti-inflammatory drug (NSAID). However, an increasing number of case reports suggest that in broad use, KP can cause allergic dermatitis. Most of these adverse effects have been attributed to the photoallergic potential of KP and photosensitivity. With the exception of a few reports in experimental animals, there is little evidence that KP actually causes dermal toxicity. In this study, in order to investigate the eventual underlying causes of KP dermal toxicity, we conducted primary irritation, skin cumulative, skin sensitization, phototoxicity and photosensitization tests in rodents and rabbits. Primary irritation and skin cumulative testing using New Zealand white rabbits revealed that application of KP (22, 15 and 10%) did not induce erythema or edema formation. Moreover, in skin sensitization and skin phototoxicity testing, using Hartley albino guinea pigs, there was no evidence of allergic or phototoxic potential. In the photosensitization test, KP induced skin reactions in six of eight guinea pigs with signs of erythema on the application site. Histologically, in photosensitized skin, epidermal hyperplasia, including incremental stratum granulosum, acanthosis, keratinocyte hypertrophy and dermal inflammatory cell infiltration, was observed. In this animal study, no primary irritation, cumulative irritation, skin sensitization or skin phototoxicity was observed with KP treatment. However, we identified photosensitization as the underlying cause of KP dermal toxicity.