雷帕鸣 Rapamune

【药品名】

西罗莫司 Sirolimu

【性状】

西罗莫司的其化学名称为 ：(3S, 6R, 7E, 9R, 10R, 12R, 14S, 15E, 17E, 19E, 21S, 23S, 26R, 27R, 34aS)-9, 10, 12, 13, 14, 21, 22, 23, 24, 25, 26, 27, 32, 33, 34, 34a-十六氢-9, 27-二羟基-3-[(1R)-2-[(1S, 3R, 4R)-4-羟基-3-甲氧环己基]-1-甲基乙基]-10, 21-二甲氧-6, 8, 12, 14, 20, 26-六甲基-23, 27-环氧-3H-吡啶并[2, 1-c][1, 4]氧杂氮杂三十一环烯-1, 5, 11, 28, 29 (4H, 6H, 31H)-戊酮。分子式 ：C51H79NO13，分子量 ：914.2。

【适应症】

适用于接受肾移植的患者，预防器官排斥。

【作用机制】

西罗莫司抑制由抗原和细胞因子（白介素IL-2、IL-4和IL-15）激发的T淋巴细胞的活化和增殖，它亦抑制抗体的产生。在细胞中，西罗莫司与免疫嗜素，即FK结合蛋白-12（FKBP-12）结合，生成FKBP-12免疫抑制复合物。此复合物与哺乳动物的西罗莫司BA分子（mTOR，一种关键的调节激酶）结合并抑制其活性，从而抑制细胞周期中G1期向S期的发展。

【药代动力学】

服用西罗莫司口服溶液后迅速吸收，单剂量口服后的平均达峰时间约为1小时；在肾移植受者中，多剂量口服后的平均达峰时间约为2小时。高脂肪餐可增加西罗莫司的吸收，故建议口服西罗莫司片剂时应恒定地与或不与食物同服。西罗莫司分布容积（Vss/F）的平均值为12±8 L/kg。西罗莫司与人血浆蛋白广泛结合（约92%）。西罗莫司为细胞色素P450 III A（CYP3A）和P-糖蛋白（P-gp）的作用底物。西罗莫司可被肠壁和肝脏中的CYP3A4代谢，并且可被P-gp从小肠上皮细胞逆转运至肠腔。因此，作用于上述两种蛋白的药物可影响西罗莫司的吸收和清除。CYP3A和P-gp的抑制剂可增加西罗莫司的浓度（地尔硫卓、甲氧氯普胺、西柚汁、酮康唑、伏立康唑、伊曲康唑、红霉素、泰利霉素和克拉仙霉素）；CYP3A和P-gp的诱导剂可降低西罗莫司的浓度(卡马西平、苯巴比妥、苯妥英、利福布丁、利福平、利福喷丁、圣约翰草[St. John’s Wort]（贯叶连翘，金丝桃素）)。西罗莫司与以上两种蛋白的抑制剂或诱导剂合用时，注意监测药物浓度。西罗莫司主要经粪便排泄，仅少量（2.2%）经尿排泄。

【用法】

肾移植患者的建议负荷量为6 mg，维持量为2 mg/天。研究表明儿童患者应在每天一次性服用环孢素后16小时服用西罗莫司。
1、雷帕鸣与环孢素合用在一项单剂量药物-药物相互作用试验中，24例健康志愿者同时或在服用环孢素胶囊300 mg四小时后服用西罗莫司片剂10 mg。联合服用时，西罗莫司的平均Cmax和AUC，分别比单独服用西罗莫司上升了512%和148%。但在服用环孢素胶囊4小时后服用，西罗莫司的Cmax和AUC比单独服用西罗莫司均上升了33%。故建议服用环孢素4小时后服用西罗莫司。2、特殊人群用法由于西罗莫司主要经肝脏排泄，过对于轻至中度肝功能损害的患者，推荐调整剂量，建议剂量减少1/3。肾功能损害对于西罗莫司药动学的影响尚不清楚。但此药物或其代谢物从肾脏排泄极少（2.2%）。

【不良反应】

很常见（依据国际医学组织理事会频数分类指发生率≥10%）：淋巴囊肿、外周性水肿、腹痛、腹泻、低血钾、乳酸脱氢酶升高、痤疮，尿路感染；在较高剂量时很常见：贫血、高胆固醇血症、血小板减少症、高甘油三酯血症（高脂血症）。在阴凉、干燥、避光的环境中保存。

规格：雷帕鸣 1毫克/毫升，60毫升口服溶液/瓶
生产厂家：惠氏公司

Treatment options are limited for orthotopic liver transplant (OLT) recipients suffering from chronic rejection (CR). We performed a retrospective review of OLT recipients diagnosed with CR and treated with sirolimus. The medical records of all OLT recipients treated with sirolimus between October, 1998 and October, 2000 were retrospectively reviewed. The diagnosis of CR was made by both clinical and histologic criteria: bile duct to hepatic artery ratio less than 0.7, histologic activity index,hepatic arterial wall thickening, and chronic elevation of liver chemistries. Two groups were defined in regard to sirolimus response: sirolimus responders (SR) and sirolimus nonresponders (SNR). Response to treatment was granted only when patientswere found to have resolution of abnormal liver transaminases and an improvement in hepatic artery to bile duct ratio. Serum collections for liver chemistries were collected on days 1, 30, 60, and 90. Liver biopsies were reviewed in blinded fashion from day 1 and at least 180 days on therapy by double-blinded pathologists. Sirolimus-related complications were recorded and include drug toxicity, anemia with and without treatment, hospitalizations, infections, immunosuppression complications, lipid profile disorders, edema, muscle aches, and gastrointestinal complaints. Twenty-one patients were diagnosed with CR. The SR group included 13 of 21, and 8 of 21were in the SNR group. Anemia was diagnosed in 12 of 21 patients: SR, 7 of 13; SNR, 5 of8; with 5 patients requiring red blood cell transfusions (2 SR, 3 SNR).

Generic name
Sirolimus (May also be called Rapa or Rapamycin)

Brand name
Rapamune®

*This drug is not available as a generic.*

Use
Sirolimus suppresses the immune system to keep your transplanted organ from rejecting.

Dose
Sirolimus is available as 1 mg and 2 mg tablets along with an oral liquid. It is usually dosed once daily but may be dosed twice daily. A blood test is required to assess the dose needed for each patient. Dosages vary per patient based on blood test values. Your physician will decide on the appropriate dose for you.

Instructions
Your sirolimus dose should not be taken before your blood test on clinic days. Please bring your sirolimus dose with you to take after your blood is drawn. There are many drug interactions and some food interactions with sirolimus. Please call your coordinator before starting any new medications.

Side effects
Sirolimus can cause stomach upset or diarrhea. It can also cause an increase in cholesterol levels or changes in blood counts. Sirolimus can also cause mouth ulcers or a rash. Please notify your coordinator if you experience any of these side effects.