Yonezawa Yutaka, Ohsumi Tomoka, Miyashita Taishi, Kataoka Akira, Hashimoto Kazuto, Nejishima Hiroaki, Ogawa Haruko
Pharmacokinetics and Safety Department Drug Research Center Kaken Pharmaceutical Co., Ltd.
J Toxicol Sci. 2015 Dec;40(6):667-83. doi: 10.2131/jts.40.667.
Guinea pigs are the most frequently used animals in phototoxicity studies. However, general toxicity studies most often use Sprague-Dawley (SD) rats. To reduce the number of animals needed for drug development, we examined whether skin phototoxicity studies could be performed using SD rats. A total of 19 drugs that had previously been shown to have phototoxic potential and 3 known phototoxic compounds were administered transdermally to guinea pigs and SD rats. Eleven of the potentially phototoxic drugs and 2 of the known phototoxic compounds were also administered orally to guinea pigs and SD rats. After administration, the animals were irradiated with UV-A (10 J/cm(2)) and UV-B (0.25 J/cm(2) in guinea pigs and 0.031 J/cm(2) in SD rats) with doses based on standard phototoxicity study guidelines and the results of a minimum erythema dose test, respectively. In the transdermal administration study, all of the known phototoxic compounds and 7 of the drugs induced phototoxic reactions. In the oral administration study, both known phototoxic compounds and 5 drugs induced phototoxic reactions in both species; one compound each was found to be toxic only in SD rats or guinea pigs. The concordance rate of guinea pigs and SD rats was 100% in the transdermal administration study and 85% in the oral administration study. This study demonstrated that phototoxicity studies using SD rats have the same potential to detect phototoxic compounds as studies using guinea pigs.
豚鼠是光毒性研究中最常使用的动物。然而，一般毒性研究最常使用的是斯普拉格-道利（SD）大鼠。为了减少药物研发所需的动物数量，我们研究了是否可以使用SD大鼠进行皮肤光毒性研究。将总共19种先前已证明具有光毒性潜力的药物和3种已知的光毒性化合物经皮给予豚鼠和SD大鼠。其中11种具有潜在光毒性的药物和2种已知的光毒性化合物也经口给予豚鼠和SD大鼠。给药后，根据标准光毒性研究指南和最小红斑剂量试验结果，分别用UV-A（10 J/cm²）和UV-B（豚鼠为0.25 J/cm²，SD大鼠为0.031 J/cm²）对动物进行照射。在经皮给药研究中，所有已知的光毒性化合物和7种药物均引发了光毒性反应。在口服给药研究中，两种已知的光毒性化合物和5种药物在两种动物中均引发了光毒性反应；各有一种化合物仅在SD大鼠或豚鼠中显示有毒性。在经皮给药研究中，豚鼠和SD大鼠的一致性率为100%，在口服给药研究中为85%。本研究表明，使用SD大鼠进行光毒性研究与使用豚鼠进行研究在检测光毒性化合物方面具有相同的潜力。
