Kanie Shohei, Fujieda Mitsuhiro, Hitotsumachi Tomoaki, Suzuki Satoshi, Morita Fumio, Hakoi Kazuo, Yasui Hirofumi
Toxicology Laboratory, Discovery and Preclinical Research Division, TAIHO Pharmaceutical Co., Ltd.
Discovery and Preclinical Research Division, TAIHO Pharmaceutical Co., Ltd.
J Toxicol Sci. 2017;42(3):291-300. doi: 10.2131/jts.42.291.
S-1 is an anticancer agent that consists of tegafur, gimeracil, and oteracil potassium at a molar ratio of 1:0.4:1. S-1 is used to treat metastatic and resectable gastric cancer. However, the extensive use of S-1 in clinical practice results in watery eyes, a serious clinical problem, which worsens patients' quality of life. Although repeated instillation of artificial tears is recommended, therapy or prophylaxis against S-1-induced ocular toxicity has not been established. In the present study, we evaluated the alleviating effects of repeated artificial tear instillation on S-1-induced ocular toxicity in dogs. Ten beagle dogs (5 males and 5 females) were orally administered 3 mg/kg/day of S-1 for up to 21 days. Five drops of artificial tears were instilled to the left eye, eight times daily, within 6 hr after S-1 administration. The mean cornea staining score tended to be low in the left eye with repeated artificial tear instillation. In 4 out of 10 dogs, the corneal staining score of the left eye was more than 2-fold lower than that of the right eye. The incidence of dogs indicating normal tear drainage increased and stenosed tear drainage decreased by repeated artificial tear instillation. In conclusion, we demonstrated that artificial tear instillation can alleviate corneal surface damage induced by S-1 in dogs.
S-1是一种抗癌药物,由替加氟、吉美嘧啶和奥替拉西钾按1:0.4:1的摩尔比组成。S-1用于治疗转移性和可切除的胃癌。然而,S-1在临床实践中的广泛使用导致流泪,这是一个严重的临床问题,会恶化患者的生活质量。尽管建议反复滴注人工泪液,但尚未确立针对S-1诱导的眼部毒性的治疗或预防方法。在本研究中,我们评估了反复滴注人工泪液对S-1诱导的犬眼部毒性的缓解作用。十只比格犬(5只雄性和5只雌性)口服给予3mg/kg/天的S-1,持续21天。在给予S-1后6小时内,每天8次向左眼滴入5滴人工泪液。反复滴注人工泪液后,左眼的平均角膜染色评分趋于降低。在10只犬中有4只,左眼的角膜染色评分比右眼低2倍以上。反复滴注人工泪液后,泪液引流正常的犬的发生率增加,泪液引流狭窄的犬的发生率降低。总之,我们证明了滴注人工泪液可以减轻S-1诱导的犬角膜表面损伤。