- Yutaka Yonezawa (Pharmacokinetics and Safety Department Drug Research Center, Kaken Pharmaceutical Co., Ltd. / firstname.lastname@example.org)
1) Pharmacokinetics and Safety Department Drug Research Center, Kaken Pharmaceutical Co., Ltd. , 2) Kumamoto Laboratory, LSI Medience Corporation , 3) Drug Safety Research and Evaluation, Takeda Pharmaceutical Company Limited.
The Sprague-Dawley (SD) rat has been widely used for general toxicity and toxicokinetic (TK) studies, and is also useful for phototoxicity assessments. We previously showed that phototoxicity assessments could be incorporated into general toxicity study. However, this research was performed at only one facility. Thus, the effects of repeated administration and TK blood collection were investigated in three facilities to explore the possibility of incorporating phototoxicity assessments into general toxicity study. Lomefloxacin and pirfenidone were tested as the phototoxic compounds. Six-week-old male and female SD rats were allocated to two groups for each compound: single-dose and repeated-dose. The single-dose group was irradiated after a single administration of the drug without blood collection for TK. The repeated-dose group was irradiated after 8 days of repeated administration of the drug with TK blood collection (total 0.72-0.84 mL) after the 1st and 7th administration. Phototoxic reactions on the ventral skin, dorsal skin, and auricle skin were observed macroscopically at 2, 24, 48, and 72 hr after irradiation, and skin reaction scores were evaluated. The phototoxic compounds produced skin reactions in rats at all facilities regardless of the presence or absence of repeated administration and TK blood collection. However, there were differences in the degree of skin reaction between the two groups and among the facilities. Although further studies are needed to standardize this new evaluation system, we expect that the incorporation of phototoxicity assessments will contribute to shortening the research and development period and support the 3R principle for animal experiments.