29．1，6-二磷酸果糖
出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第157页（10497字）
【中文释文】：
〔说明〕
国际命名：1，6-Fructose-Diphosphate(FDP) 1，6-二磷酸果糖
性状：本品系冻干粉剂，包装可保持5年。一般室温(约25℃)下即可保存。
作用简介：FDP系1，6-二磷酸果糖钠盐，具调节糖代谢中若干酶活性之功效，为恢复、改善细胞代谢的分子水平药物。药品系冻干粉剂，经稀释后供胃肠道外使用。每克本品含净化学药品，1，6-二磷酸果糖0．75g。每5g本品含23mmol无机磷。
〔实验资料〕
药效学、药物动力学及临床药理学研究。
外源性FDP通常无法跨越细胞膜，但可作用于细胞膜，通过刺激磷酸果糖激酶的活性，聚增细胞内高能磷酸池，细胞内ATP浓度，促进钾离子内流，回复细胞极化状态，从而有益于休克、缺氧、缺血、损伤、体外循环、输血等状态下的细胞能量代谢及对葡萄糖的利用，以促进修复、改善功能。
增加红细胞内的二磷酸甘油酯，有益于红细胞向组织释放氧气。
体外实验发现FDP可增加红细胞韧性及抗溶血的能力，防止白细胞产生有害的氧自由基，抵制因正定霉素及各种不良刺激作用于干细胞而造成的组胺释放作用，从而减少细胞损伤。
FDP拮抗氯化钾对实验鼠心肌的毒性作用，并对实验犬的失血性休克及创伤性休克状态有明显的保护作用。
用同位素标记的FDP(14℃)经静脉输入实验鼠，可见分布于肾脏、肝脏、回肠、肌肉、心脏及大脑等脏器。
临床药理研究发现用250mg／kg的剂量，给健康志愿者静脉输注FDP，5min内其血浆浓度可达770mg／L，其半衰期约10～15min，并通过向血管外组织分布，并经水解形成无机磷及果糖而从血浆中消失。
急性毒性试验表明，以0．4g／(kg·min)或0．6g／(kg·min)的速度静脉输注FDP，实验鼠与实验兔的致死量分别为5．0g／kg和5．8g／kg。急性毒性效应似乎和大剂量FDP水解后造成大量无机磷进入体循环所致毒性有关。
急性毒性试验表明，以100mg／kg和200mg／kg的剂量分别给实验犬和实验兔输注FDP共30d，未发现有形态和功能方面的病理改变。
适应证：休克，心肌缺血，心肌梗塞，急性成人呼吸窘迫综合征，心脏外科体外循环辅助治疗，外周血管病变，危重病例如各种复合伤、烧伤等，麻醉意外，围产期辅助治疗，胃肠外营养疗法，多次输血辅助疗法。
〔临床应用〕
1．休克、急性心肌梗塞及心肌缺血 临床资料证实FDP可增加无氧碳水化合物利用，防止白细胞产生的毒性氧自由基对组织的损害。最近的临床资料证明FDP对急性心肌梗塞特别合并心力衰竭及外周低灌注者有明显疗效，左心室作功指数明显回升有益于缺血心肌改善心脏作功指数达24%，改善缺血性心电图改变，并预防室性心律失常的发生。
FDP与洋地黄可起到协同作用。增加利尿，减慢心率，使单用洋地黄无效或难治性心力衰竭病人获益。每日4～6瓶，分2～3次用完。用2～7d。
2．心脏直视手术，体外循环 FDP可有效地防止体外循环对红细胞的损伤。临床资料证明，治疗组发生的溶血较对照组下降1／3。用红细胞滤过技术检测发现，对体外循环病人应用20g／d的FDP可减少红细胞膜的僵硬度，并增加细胞内ATP的产生。每12h1次，每次2瓶，自术前1d始至术后48h，共3d。
3．外周血管疾病 FDP改善缺氧细胞对葡萄糖的利用，有益于红细胞释氧的能力及对血液流变学的影响，可用于外周血管疾患。临床资料证明本品可增加缺血性下肢的节段供血，改善肌肉功能，减轻休息中及运动后的肢体疼痛。每日2瓶，用5～7d。
4．重危病人接受胃肠外营养疗法中重危病人诸如复合外伤，大面积烧伤等接受胃肠外营养疗法中，本品可改善氮平衡，使尿素氮和血糖恢复正常，减少外源性胰岛素的用时，增加细胞内二磷酸甘油酯浓度，从而增加红细胞的释氧作用。每日2～4瓶，用3～7d。
5．用于多次输血的病人 维持红细胞正常二磷酸甘油酯浓度，有利于红细胞的释氧作用。每日2～4瓶，用3～5d。
〔用法〕
瓶装，每瓶5g，包装内配有50ml无菌，无致热源的双蒸馏水及静脉输注针头皮管。本品充分溶匀成10%溶液后供静脉滴注。药瓶及全套输液装置均为一次性使用装置。
安瓿。每支0．5g，用时稀释于4支(每支5m1)共20ml无菌、无致热源的双蒸馏水中，供静脉滴注。
单次剂量。一次剂量为100～250mg／kg体重。静滴速度为5gFDP以5～10min滴完。
〔注意〕
本品宜单独使用，勿溶入其他药物，尤其忌溶入碱性液、钙盐等。
本品禁用于对本品过敏及高磷酸症，高磷血症，肾功能衰竭病人。肌酐清除率低于50%者务必监测血磷。
〔药品保存〕
保存于常温下(30℃以下)。包装完整者，有效期5年。
〔FDP输液装置〕
本装置包括：双尖头溶剂引流管，带滤网壶腹输液塑条，控制滴速金属软夹片，输液瓶塑料吊托，输液针头。
〔用法指导〕
1．配制溶液。打开包装后，将双尖头引流管的一头先插入溶剂瓶中，再将另一头插入FDP冻干粉瓶中，使溶剂瓶在上，粉瓶置桌上，双手将二瓶拿稳，轻摇粉瓶，溶剂自上而下流入粉瓶。溶剂流完后，拔出引流管，充分溶匀FDP溶液。
2．输液装置。去除壶腹部近端锐管头上的套子，并将之插入液体瓶。用金属软夹片夹牢输液管。将塑料吊托套好液体瓶，挂上输液架。将输液塑管接上输液针头，小心排气泡后进行静脉穿刺输注。以软夹片调节调速。
3．充分溶解的溶液可置常温下(勿超过30℃)保存24h。但切勿重复使用，切勿溶入其他药物。
4．本装置为无菌、无致热源、一次性使用装置，用毕请丢弃。包装一旦受损，切勿使用。
〔生产厂家〕
意大利罗马 福斯卡玛生化制药公司
(附本品别名：依福那)
【外文释文】：
Description
Esatosfina is the sodium salt of fructose 1，6-diphosphate(FDP)a naturally occurring allosteric effector that modulates the activity of several enzymes of glucose metabolism．Esafosfina is supplied as a lyophilized powder for parenteral use containing 0．75 grams of fructose-1，6-diphosphoric acid per 1 gram．
Actions
Exogenously-administered FDP does not appear to cross the cell wall although some authors have suggested it enters into damaged cells．Available evidence would seem to indicate that the main mode of action is an interaction with the cell wall stimulating phosphofructokinase activity with a final net increase of the high-energy intracelluar phosphate pool，The primary event triggered by the interaction at the cell surface appears to be an increase of potassium influx into the cell．
In vitro studies indicate that FDP protects erythrocytes against hemolysis and prevents the production of toxic oxygen radicals in neutrophils．
Studies on isolated rabbit hearts showed that FDP antagonizes the toxic effect of potassium on atrial contractility and improves the post-arrest acrdiac performance．FDP prevents the reduction of heart ATP and creatine phosphate in dogs subjected to myocardial ischemia，protects liver and kidney from ischemic damage in rats，exerts a marked protective activity against hemorrhagic and traumatic shock in dogs and rats and facilitates successful resuscitation following circulatory arrest in rabbits．In rats receiving intravenous doses of radiolabelled FDP(14℃)the drug appears to distribute with decreasing affinity in the following organs：kidney，liver，ileum，muscles，lung，heart and brain．
Clinical studies have shown that FDP increases intra-erythrocytic 2．3-DPG in patients receiving multiple transfusions；lowers elevated plasma potassium concentrations restoring the correct intracellular to extracellular potassium ratio and improves erythrocyte flexibility and resistance to mechanical hemolysis during extracorporeal circulation；affects positively nitrogen balance in total parenteral nutrition，improves the hemorhelolgical pattern in patients with peripheral vascular disease and improves the hemodynamics in acute myocardial infarction．
Pharmacokinetics
Following intravenous infusion of a single 250 mg／kg dose of Esafosfina to normal volunteers，mean plasma concentration of 770 mg／l were recorded within 5 minutes of infusion and declined with an elimination half-life of 10-15 minutes．Disappearance of FDP from plasma is due to its distribution to the extravascular compartment and its hydrolysis into phosphorus and fructose caused by the activity of plasmatic and membrane-bound erythrocyte phosphatases．
Indications and usage
Recent clinical data indicate that Esafosfina(FDP)is beneficial in patients with myocardial infarction，in the treatment of shock and regional ischemia and in severe ischemia of lower limbs．Esafosfina is indicated in hypophosphatemia associated with metabolic impairment (malabsormption，severe burns and total parenteral nutrition)，in 2．3-diphosphoglycerate depletion following multiple transfusions，and during extracorporeal circulation in cardiac surgery．
Contraindications
Known hypersensitivity to the drug，hyperphosphatemia，renal insufficiency．
Warnings
In patients with ceatinine clearance below 50 ml／min phosphatemia should be moni
tored．
Precautions
General：Extravasation in the subcutaneous tissue during infusion causes mild local pain and irritation．
Compatibility：Do not mix Esafosfina with other drugs insoluble at pH 5．5 or with alkaline solution of calcium salts．
Drug interactions：No drug interactions have been reported．
Overdosage：No overdosage symptoms have been reported．
Adverse reactions
Esafosfina appears to be well tolerated．
Dosage and administration
Esafosfina intravenous infusion：
Esafosfina 5 grams once reconstituted with 50 ml of solvent to yield a 10%solution should be given as a rapid intravenous infusion at a rate of about 1 gram per minute．The recommended daily dose for single intravenous infusion is 70-160 mg／kg b．w．up to a maximum of 250 mg／kg b．w．One gram of Esafosfina delivers 4．6-4．8 mmol of inorganic phosphate．
Esafosfina ampuls：
One-two ampuls／day(0．5-lg)intravenously．
How supplied
Vials：Unit packages of a single dose vial of Esafosfina for intravenous infusion containing 5 grams of fructose-1．6-diphosphate sodium salt lyophilized powder equivalent to 3．75 g of fructose-1，6-diphosphoric acid plus one vial of 50ml of sterile，pyrogen-free bidistilled water．The two vials are accompanied by an infusion set．Ampuls：Boxes of 4 vials each containing 0．5g of fructose-1．6-diphosphate sodium salt lyophilized powder equivalent to 0．375 g of fructose-1．6-diphosphoric acid plus 4 vials of 10ml of sterile，pyrogen-free bidistilled water．
Pharmaceutical information
Shelf life：Intact package 5 years．
Stability：Esafosfina，once reconstituted，is stable for at least 24 hours at room temperature．If not completely infused，do not reuse the remaining quantity of the solution．
Special conditions for storage：Store at room temperature below 30℃(86°F)．References are available upon request．
Administration set to deliver esafosfina 5g infusion
The administration set includes：a double tipped plastic spike to transfer the solvent from the small container to reconstitue the powder in the large container，and infusion line with vented drip-chamber，an adjustable clamp，a rubber injection port，a plastic bottle strap and a needle．
Directions for use
Double-tipped spike：
1．Remove aluminium tear seals on both powder and solvent container．
2．Wipe closures with disinfectant．Remove one protection cap of the double-tipped spike and insert one and in the targel area of the powder bottle．
3．Remove the other protection cap and insert the second end of the spike in the target area of the solvent bottle．
4．Hold the two bottles with the solvent container on top and shake gently to allow the solvent to drip into the power bottle
5．Remove the spike and solvent bottle and shake the powder container well to insure adequate reconstitution．
The material contained in this package is sterile，pyrogen-free and disposable．
To be used immediately after removing protection caps．
Do not use if packaging damaged．
Do not reuse．
Manufacturer
Biomedica Foscama
Chemical-phamaceutical company S．P．A．
Joint phamaceutica Plant
Biomediea Foscam-I．R．F．I．
Ferentino-Italy