英文药名：TS-1 combination OD tablet（Tegafur/Gimeracil/Oteracil Potassium） 中文药名：替吉奥（复合替加氟/吉美嘧啶/氧嗪酸钾口腔崩解片） 生产厂家：大鹏药业 ティーエスワン配合OD錠T20／ティーエスワン配合OD錠T25 治疗类别名称 代谢拮抗剂 商標名 TS-1 combination OD tablet T20 TS-1 combination OD tablet T20 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。微溶于甲醇，微溶于水或乙醇（95）。溶于稀氢氧化钠TS中。甲醇溶液（1→50）示出了没有旋光性。水晶多态性观察。 吉莫斯特 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。钠试剂或N氢氧化物，N-二甲基甲酰胺，以容易难溶，难溶在甲醇中，在乙醇（99.5）微溶，在极微溶于水。 奥替拉西钾 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的磷酸盐缓冲溶液或水，和在乙醇（99.5），甲醇几乎不溶。 操作注意事项 打开后，保存，以避免水分。 条件批准 1.根据所提交的实施计划，经过数据的适当商业研究收集关于（专项调查和上市后的临床试验）是阶乘和信息安全关系到代理商的血药浓度波动的程度，等等它落到实处，尽快提交结果。 2.执行足够的样本大小的随机对照试验进一步澄清该代理结直肠癌的疗效和安全性的目的。 3.在与此试剂和组合，非小细胞功效为肺癌，和安全抗癌剂以及澄清联合治疗的临床定位，对于非小细胞肺癌未处理示例的标准含铂相比于对照组的抗肿瘤剂的联合治疗，进行第三阶段的随机对照试验中的存活和主要终点。 药效药理 1.抗肿瘤作用 吉田肉瘤，腹水肝癌AH-130，佐藤肺癌（大鼠）和肉瘤180，Lewis肺癌，各种皮下移植肿瘤，如将Colon26（小鼠），另外，人胃癌，结肠癌，乳腺癌，肺癌，胰腺癌，肾癌皮下到移植瘤（裸大鼠或裸鼠），它显示出肿瘤生长的抑制作用。 此外，在Lewis肺癌（鼠）肝转移模型的肺转移模型和L5178Y显示了生存利益，也TS-1肿瘤生长的抑制作用与原位重建人胃癌和结肠癌线进一步模型（裸大鼠）它被示出。 2. TS-1作用机构 TS-1是FT，含有CDHP和氧的三种组分的制剂中，口服给药后的抗肿瘤作用是基于5-FU被逐渐从FT在体内转化。 CDHP主要通过选择性地拮抗5-FU分解代谢酶的DPD来增加分配到肝脏，增加从FT衍生的5-FU的浓度。在体内的5-FU与肿瘤内增加浓度，在5-FU的5-氟核苷酸的磷酸化代谢物重持续的抗肿瘤效果提高。此外，氧选择性通过口服给药拮抗主要分布在消化道组织乳清酸磷酸，选择性地抑制产生由5-FU向5-氟核苷酸。胃肠道毒性被认为是未经受的结果的TS-1给药影响的5-FU的很强的抗肿瘤效果降低。 的5-FU作用的机理主要是活性代谢物FdUMP是拮抗转储，通过DNA生物合成抑制剂由于胸苷酸合成酶的形成和还原叶酸盐和三元复合物。此外，它也表示，转换为FUTP故障RNA的功能。 适应病症 胃癌，大肠癌，头颈部癌，非小细胞肺癌，不能手术或复发性乳腺癌，胰腺癌，胆道癌。 用法与用量 通常情况下，按照初始剂量（量一次）体表面积作为下一个参考量，早餐后和两次晚饭后一天的成年人，每天连续28天口服给药，然后停药14天。重复给药，本为一疗程。 （表1） 所述剂量可根据病人的情况进行调整。以增加或减少阶段的量的40毫克，50毫克，60毫克和75毫克/次。初始如果延长临床实验室异常（验血，肝，肾功能检查）被确定为是由于这种药物和不表达消化系统症状的施用，存在安全性没有问题，则确定可以增加与从基准量的一个步骤，它被限制为75毫克/次。此外，减肥通常进行一步一步的最低剂量和40毫克/次。 用法与用量的表 1表 体表面積  初回基準量（テガフール相当量）  1.25m2未満  40mg/回  1.25m2以上～1.5m2未満  50mg/回  1.5m2以上  60mg/回 包装规格 混合OD片：T20 PTP包装：56片（14片×2×2），140片（14粒×2×5） 混合OD片：T25 PTP包装：56片（14片×2×2），140片（14粒×2×5） 制造厂商 大鹏药业有限公司 完整处方资料附件：http://www.info.pmda.go.jp/go/pack/4229101F1026_1_03/ 复方替加氟胃滞留型缓释片TS-1 combination OD tablet（Tegafur/Gimeracil/Oteracil Potassium） 替加氟(tegafur)为5-氟尿嘧啶(5-FU)的衍生物,口服后经肝脏活化为5-FU而发挥其抗肿瘤活性,其化疗指数为5-FU的两倍,毒性仅为5-FU的1/4~1/7。但5-FU口服后在肝二氢嘧啶脱氢酶(DPD)的作用下迅速降解,在消化道的乳清酸磷酸核糖转移酶(ORPT)的作用下生成磷酸化物而导致严重的胃肠道不良反应。 日本大鹏制药有限公司于1991年开始研制替加氟的复方制剂(S-1胶囊)[1],该制剂含有3个有效组分:替加氟、吉美嘧啶(gimeracil)和氧嗪酸钾(potassium oxonate)(物质的量之比为1∶0·4∶1)。其中吉美嘧啶可强烈抑制DPD的活性,阻止5-FU降解,氧嗪酸钾可保护胃肠道黏膜,减少消化道不良反应达80%,主要用于胃癌的治疗,一日两次,饭后服用。 该药自1999年1月上市以来,由于其疗效确切,不良反应小,是迄今为止单药治疗胃癌最有效的药物。 为了增加其在胃内的局部浓度,提高靶向性,降低不良反应,减少服药次数,本研究将该复方制剂制成一日一次的胃内滞留型缓释片,以期取得更好的结果。 TS-1 combination OD tablet T20/T25（Tegafur/Gimeracil/Oteracil Potassium） Effects of this medicine TS-1 enhances the antitumor activity in proportion to the increase in the concentration of 5-fluorouracil (5-FU) in the body via the biotransformation of FT to 5-FU. Also, this medicine relieves gastrointestinal toxicities (side effects) through the effects of oteracil pottasium. This drug is commonly used in the treatment of gastric cancer, colorectal cancer, head and neck cancer, non-small cell lung cancer, unresectable or recurrent breast cancer, pancreatic cancer, or biliary tract cancer. Before using this medicine, tell your doctor/pharmacist If you ever experienced any allergic reaction (itch, rash etc.) to any medicine. If you present a condition indicative of bone marrow suppression (including leukopenia). If you have renal or hepatic dysfunction. If you have an infectious disease or diabetes. If you have a current or past history of interstitial pneumonia. If you have a heart disease or a history of heart disease. If you have gastrointestinal ulcers or hemorrhage. If you are using fluoropyrimidine-group anti-cancer drugs. (TS-1 and these medicines may interact strongly with each other and cause serious side effects.) If you use TS-1 after withdrawal of other fluoropyrimidine-group anti-cancer drugs. (An appropriate washout period must be provided in consideration of the influence of these prior agents.) If you are pregnant or breastfeeding. If you are using any other prescription or nonprescription (OTC) medicine. (It is important to reduce the risk of drug interactions.) Dosage regimen (proper use of this medicine) Your dosage regimen is:(order of your doctor) General dosage regimen: For adults, the initial dose is determined based on body surface area. This medicine is administered 40 mg of Tegafur for patients with under 1.25 m2 of body surface area; 50 mg of Tegaful for patients with 1.25 to 1.5 m2 of body surface area; 60 mg of Tegaful for patients with over 1.5 m2 of body surface area; twice daily after breakfast and dinner, for 28 consecutive days (4 weeks), followed by a 14-day (2 weeks) rest. This 6-week period is regarded as one course, which is repeated. The dose can be decreased or increased according to the patient's condition. Adjustment of the dose is determined 40, 50, 60, or 75 mg in incremental steps. The maximum dose is limited to 75 mg at a time, and the minimum dose is 40 mg at a time. This medicine contains 20 mg of Tegafur in a capsule. Strictly follow the instructions of your doctor/pharmacist. TS-1 must NOT be taken with other fluoropyrimidine-group anti-cancer drugs. Record your drug consumption, your physical condition and symptoms and show your records to your physician or pharmacist on your next visit. Missed dose: Proceed with the prescribed schedule of medication starting from the next dose. DO NOT take a double dose to make up for the missed dose. Overdose: If you took too much of this medicine (more than ordered), check with your doctor/pharmacist. Others: Do not change your dose and schedule of your chemotherapy without the instructions of your doctor. Precautions while using this medicine During the treatment, laboratory tests (hematological, liver and renal function tests) are performed regularly at least once every 2 weeks to detect asymptomatic side effects as early as possible. Be sure to consult your doctor. Side effects of this medicine Common side effects are reported as below. If any of them occurs, check with your doctor/pharmacist: anorexia, nausea, vomiting, diarrhea, tiredness, stomatitis, pigmentation, rash, lacrimation, etc.In rare cases, symptoms described below may be the sign of side effects indicated in brackets[ ]. If they occur, stop taking your medicine and check with your doctor immediately. bleeding tendency, tiredness, fever, sore throat[bone marrow suppression] yellowing of the skin, tiredness, yellowing of the whites of the eyes, anorexia[severe hepatic dysfunction] diarrhea, severe abdominal pain[severe enteritis] difficult breathing, fever, dry cough[interstitial pneumonia] blood in stool, darkened stool, hematemesis, abdominal pain[gastrointestinal ulcer/gastrointestinal hemorrhage/ gastrointestinal perforation] severe stomatitis, red rash, eyelid or eye redness[muco-cutaneo-ocular syndrome] Other side effects not listed here may occur. Check with your doctor/pharmacist if you have any worrisome symptom.  Storage and other information Keep the medicine out of the reach of babies, infants, and children. Store away from direct sunlight, heat, and humidity. Discard the remainder. Do not store them. Check with the pharmacy regarding how to discard. For further information, ask your doctor/pharmacist. "Kanjamuke Iyakuhin Guide" and Japanese package insert information (for medical professionals) is available on the website of Pharmaceuticals and Medical Devices Agency.