EXPERIMENTAL TESTING OF AN IN VIVO METHOD OF PHOTOTOXICITY EVALUATION

Abstract

At present all new medicinal products and cosmetics that absorb medium-wavelength UVB, long-wavelength UVA, or visible light in the range 290–700 nm need to be tested for potential phototoxicity. phototoxicity is evaluated by both in vitro and in vivo methods. There are guidelines for in vitro phototoxicity evaluation, however, there are no formally validated protocols for in vivo phototoxicity evaluation. The purpose of this study was to test an economically viable and informative method for in vivo evaluation of tetracycline and ketorolac phototoxicity using outbred rats. Two medicinal products potentially capable of causing clinically established phototoxic reactions were used in this study: tetracycline (tablets, 200 mg/kg and 300 mg/kg) and ketorolac (gel, 13.4 mg/kg, 26.8 mg/kg and 40.3 mg/kg). The medicines were administered in both single and multiple doses. Ultraviolet irradiator OUFK-03 (OOO «Solnyshko», Russia) was used as a light source. The UV exposure (5 J/cm2 and 15 J/cm 2 ) was performed once 1 h after medicine administration. The skin reaction was evaluated 30 minutes and 24 hours after irradiation and then daily for 2 weeks. As a result, the following optimal parameters were determined for in vivo evaluation of phototoxic reactions caused by the medicines: radiation intensity — 15 J/cm 2 for single systemic administration and 5 J/cm 2 for single topical (dermal) administration; recommended period of skin reaction evaluation for outbred rats is not less than 7 days.