抄録
Phototoxicity sometimes has a strong impact on drug development. However, there is no validated in vivo system likes as 3T3 NRU PT test in vitro. This study focused on the usefulness of an in vivo phototoxicity model using Long-Evans (LE) rats for quantitative human risk assessment. Three phototoxic drugs for human, nabumetone, chlorpromazine and promethazine were selected because there were no positive results of these compounds in vivo phototoxicity reports using animals. Nabumetone (2000 mg/kg), chlorpromazine (40 mg/kg) and promethazine (200 mg/kg) were administrated once orally to female LE rats. The skin and eyes of LE rats were exposed by UVA at 10 J/cm2 around the Tmax of each compound. Daily observation of skin and eyes, ophthalmological examination 4 days after dosing, and blood sampling for toxicokinetics (TK) was also performed. No treatment-related phototoxic change was observed in rats with nabumetone. However, skin reaction was noted in rats treated with chlorpromazine or promethazine from Day 3. These results suggest that in vivo phototoxicity model using Long-Evans (LE) rats have enough sensitivity for human risk assessment.
