英文药名：TS-1 combination capsule T20（Tegafur/Gimeracil/Oteracil Potassium）
中文药名：吉美嘧啶+氧嗪+替加氟
生产厂家：大鵬药业
药物分类名称
抗代谢药物
批准日期：2009年9月
商標名
TS-1 combination capsule T20
TS-1 combination capsule T25
TS-1 combination granule T20
TS-1 combination granule T25
替加氟
構造式
一般名
テガフール（Tegafur）
化学名
5-Fluoro-1-[(2RS)-tetrahydrofuran-2-yl]uracil
分子式
C8H9FN2O3
分子量
200.17
融点
166～171℃
性状
它是一种白色结晶粉末。 它微溶于甲醇，微溶于水或乙醇（95）。 它溶于稀氢氧化钠试剂中。 甲醇溶液（1→50）显示没有旋光能。 观察到晶体多态性。
吉美嘧啶
構造式
一般名
ギメラシル（Gimeracil）
化学名
5-Chloro-2,4-dihydroxypyridine
分子式
C5H4ClNO2
分子量
145.54
融点
約262℃（分解）
性状
它是一种白色结晶粉末。 微溶于氢氧化钠试剂或N，N-二甲基甲酰胺，微溶于甲醇，溶于乙醇（99.5），极不溶于水。
氧嗪
構造式
一般名
オテラシルカリウム（Oteracil Potassium）
化学名
Monopotassium 1,2,3,4-tetrahydro-2,4-dioxo-1,3,5-triazine-6-carboxylate
分子式
C4H2KN3O4
分子量
195.17
融点
300℃以上
性状
它是一种白色结晶粉末。微溶于pH8.0的磷酸盐缓冲液或者水和乙醇（99.5），或甲醇中几乎不溶。
条件批准
1.根据所提交的实施计划，之后关于（专项调查和上市后的临床试验）适当的商业调查数据收集是阶乘信息和代理的血药浓度波动程度的安全性它落到实处，尽快提交结果。
2.执行与足够的样本大小的随机对照试验以进一步澄清该药剂用于结肠直肠癌的疗效和安全性的目的。
在与试剂和含铂的抗肿瘤剂用于肺癌和安全组合。
3.非小细胞效力以及澄清联合治疗的临床定位，标准用于非小细胞肺癌的实施例未处理作为比较对照组ABV，执行相位与生存III随机比较试验作为主要终点。
药用药理学
1.抗肿瘤作用
吉田肉瘤腹水肝细胞瘤AH-130，佐藤肺癌（大鼠）和肉瘤180，Lewis肺癌，各种皮下植入肿瘤如结肠26（小鼠），也是人类胃癌，结肠癌，乳腺癌，肺癌，胰腺癌，肾癌皮下它显示肿瘤生长抑制移植肿瘤（裸鼠或裸鼠）的作用。另外，在肺转移模型和Lewis肺癌（小鼠）的L5178Y肝转移模型表示的存活益处，也TS-1的肿瘤生长抑制效果在又模型原位重建人胃癌和结肠癌菌株（裸大鼠）结果表明。
2. TS-1的作用机制
TS-1是FT，含有CDHP和Oxo的三种组分的制剂中，口服给药后的抗肿瘤效果是基于5-FU，其逐渐地从FT在体内转化。
CDHP主要通过选择性地拮抗5-FU更分布在肝脏中，增加从FT衍生的5-FU分解代谢浓度代谢酶DPD。体内5-FU与肿瘤内增加浓度是5-FU 5-氟核苷酸的磷酸化代谢物重持续的抗肿瘤效果增强。此外，氧代选择性拮抗通过口服给药分布主要是胃肠道组织乳清酸磷酸核糖基，选择性地抑制制造的5-FU到5-氟核苷酸。胃肠道毒性被认为不受结果TS-1给药损害5-FU的强抗肿瘤效果降低。
5-FU的作用机制是主要的活性代谢物FdUMP的通过形成胸苷酸合成酶和还原叶酸和三元复合物拮抗转储，通过DNA合成的抑制。据说它还被转化为FUTP以损害RNA功能。
适应症
胃癌，结肠/直肠癌，头颈癌，非小细胞肺癌，不能手术或复发的乳腺癌，胰腺癌，胆道癌
用法与用量
通常，对于成人，将初始剂量（单剂量）调整至体表面积作为下一参考量，每天口服给药，连续28天，早餐后和晚餐后每天两次，然后停药14天。 以此作为一门课程重复管理。
（表1）
顺便提及，应根据患者的状况增加或减少。 增量/减量步骤设定为40mg，50mg，60mg，75mg /次。剂量增加被认为是由于该药物的给药没有异常的临床实验室检查（血液检查，肝/肾功能检查）和消化系统症状没有发展，没有安全问题，它仅限于参考量的一步，并限制在75毫克/次。另外，减重通常一次一步进行，最小剂量为40mg /次。
用法和剂量表
表1
包装
胶囊 T20
PTP包装：56粒（14粒×4），84粒（14粒×6），140粒（14粒×10）
胶囊T25
PTP包装：56粒胶囊（14粒×4粒），140粒胶囊（14粒×10粒）
混合颗粒T20
包装（0.2克）：56粒（28包×2）
混合颗粒T25
包装（0.25克）：56粒（28包×2）
制造供应商
大鵬药业有限公司
注：以上中文资料不够完整，使用者以原处方资料为准。
完整说明书资料附件：http://www.info.pmda.go.jp/go/pack/4229101D1025_1_09/
Tiogio Capsule (TS-1, S-1) is a compound anticancer drug developed by Japan Dapeng Pharmaceutical Co., Ltd. It is a compound preparation consisting of tegafur, gemcitabine and oxylacide potassium. For the treatment of unresectable locally advanced or metastatic gastric cancer.
Tegafur is slowly converted to fluorouracil in the body to exert anti-tumor effect; and gemcitabine can inhibit the catabolism of 5-Fu released from tegafur under the action of dihydropyrimidine dehydrogenase, and improve 5-Fu in plasma. Concentration, and prolong the retention time of effective drug concentration; oltipraz can reduce the damage of 5-Fu on the digestive tract mucosa, inhibit the phosphorylation of 5-Fu, and reduce its side effects on the gastrointestinal tract.
The superiority of Teggio capsules (TS-1, S-1) is better than other gastric cancer drugs in that it is more effective than simple surgery to reduce the risk of death in patients with gastric cancer; it can maintain a high blood concentration and improve Anticancer activity; significantly reduce drug toxicity; convenient administration.
Progress in clinical application of Tiggio capsules
Teggio capsule is an oral compound anti-tumor drug, which is based on tegafur, adding gemcitabine to prevent degradation of fluorouracil activator and enhancing anti-cancer effect; adding oltipraz potassium to protect gastrointestinal mucosa and reducing digestion Road reaction.
The three-way massage ratio is an oral capsule preparation made of 1:0:1 for the treatment of gastric cancer, colorectal cancer and head and neck cancer.
Tegafur is a prodrug of 5-fluorouracil that is absorbed in the small intestine and has excellent oral bioavailability and sustained release capacity. When tegafur enters the human body, it can be converted to 5-fluorouracil under the action of the liver mitochondrial P-450 metabolic enzyme system.
Gemexime is a reversible competitive inhibitor of dihydropyrimidine dehydrogenase, which is 180 times stronger than uracil in inhibiting ability, allowing high concentrations of 5-fluorouracil to produce metabolites through metabolic pathways and inhibiting DNA synthesis in tumor tissues. And blocking RNA function to exert anti-tumor effects.
When gimeracil is used in combination with tegafur, a high concentration of 5-fluorouracil can be maintained in plasma for a long period of time. In vitro, it was observed that gimeracil inhibits the degradation of 5-fluorouracil in human tumor cells, and it is speculated that gimeracil may also inhibit dihydropyrimidine dehydrogenase in tumors.
In addition, inhibition of dihydropyrimidine dehydrogenase can result in a decrease in the amount of α-fluoro-β-alanine aggregation, thereby reducing toxicity in drugs such as neurotoxicity.
Otaclac potassium itself has no antitumor activity and is not used as a drug alone. It can selectively inhibit the catalytic enzyme in the gastrointestinal mucosal cells, orotate phosphoribosyltransferase, thereby inhibiting the conversion of 5-fluorouracil phosphorylation to 5-fluorouracil-5'-monophosphate, thus reducing Gastrointestinal toxicity occurs.
Animal experiments have shown that in the small intestine, the production of 5-fluorouracil-5'-monophosphate and the ability of 5-fluorouracil to enter RNA is reduced by 70%, while 5-fluorouracil-5'-monophosphate in tumor tissue and bone marrow The ester is only reduced by 0 to 20%.
This may be due to the large accumulation of oltipraz potassium in the gastrointestinal tract compared to other tissues or plasma. Otacetam potassium competitively inhibits orotate phosphoribosyltransferase and inhibits the conversion of 5-fluorouracil phosphorylation to 5-fluorouracil-5'-monophosphate in the gastrointestinal tract, resulting in greatly reduced gastrointestinal toxicity.
In addition, potassium oxonate can also reduce 5-fluorouracil-5'-monophosphate in the gastrointestinal tract to form 5-fluoro-2-deoxyuridine-5'-monophosphate, thus indirectly maintaining the Tiggio capsule.
Active, local protection of the gastrointestinal tract, reducing gastrointestinal toxicity caused by 5-fluorouracil, such as diarrhea and defecation with blood.
In Japan, Tiggio Capsule was approved for the treatment of advanced gastric cancer in 1999.
It was approved for the treatment of head and neck cancer in 2001. It was approved for the treatment of colorectal cancer in 2003 and was approved for treatment in 2004. Cell lung cancer.
Years of clinical application has proven that Tiogio capsules are safe and effective anticancer drugs.
According to statistics, more than 80% of the cases of chemotherapy for advanced gastric cancer in Japan use Tiggio capsules, and the effective rate of treatment can reach 44.6%. Many reports in Japan reported that 28 cases of gastric cancer were treated with an effective rate of 53.6%; the effective rate of Tiggio capsules for gastric cancer was 46.5%.
Another 4 reports reported 90 cases, the effective rate was 38%, and it was highly effective in single drugs. Gastric cancer is one of the main malignant tumors in China, and it ranks first in malignant tumors.
About 160,000 people die each year, accounting for 23.03% of malignant tumor deaths.
Teggio capsule is an upgraded product of tegafur and eufloxacin, which is superior to tegafur, eufloxacin and 5-fluorouracil. In Japan, Tiggio capsules have been used as first-line drugs for the treatment of gastric cancer, head and neck cancer, and various advanced metastatic cancers.
The advantage of the Tiggio capsule is that the toxic side effects are less than tegafur, eufloxacin and 5-fluorouracil, and it is administered orally to facilitate clinical patients.