フルダラビン
6-アミノ-2-フルオロ-9-β-D-アラビノフラノシル-9H-プリン · フルダラビン · 9-β-D-アラビノフラノシル-2-フルオロ-9H-プリン-6-アミン · 2-フルオロ-9-β-D-アラビノフラノシル-9H-プリン-6-アミン · 2-フルオロ-9-(β-D-アラビノフラノシル)-9H-プリン-6-アミン · 9-(β-D-アラビノフラノシル)-2-フルオロ-9H-プリン-6-アミン · 2-フルオロ-6-アミノ-9-β-D-アラビノフラノシル-9H-プリン · 2-フルオロアデニン-9-Β-D-アラビノフラノシド
識別子と物理属性
| CAS No. | 21679-14-1 |
|---|---|
| 分子式 | C10H12FN5O4 |
| 平均分子量 | 285.23 g/mol |
| 単同位体質量 | 285.08733208 g/mol |
| SMILES | Nc1nc(F)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O |
| InChIKey | HBUBKKRHXORPQB-FJFJXFQQSA-N |
| PubChem CID | 657237 |
| ChEMBL | CHEMBL1568 |
| ChEBI | CHEBI:94701 |
| EC No. | 244-525-5 |
| DTXSID | DTXSID4039657 |
| 現地名 | フルダラビン |
化学・物理的性質
| XLogP | -0.6 |
|---|---|
| 極性表面積 | 140 |
| 水素結合供与体数 | 4 |
| 水素結合受容体数 | 9 |
| 回転可能結合数 | 2 |
| 重原子数 | 20 |
| 形式電荷 | 0 |
| 複雑度 | 367 |
| 医薬品 | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agents |
| Color/Form | Crystals |
| 溶解度 | Sparingly sol water, org solventsDMF：20～mg/mL、透明、微黄色DMF、DMSO、メタノール、エタノールに可溶。水に溶けにくい |
| Human Drugs | Breast FeedingLactationMilk, HumanAntineoplastic AgentsCytotoxic medicines |
| 融点 | 260 °C265-268°C |
| Collision Cross Section | 164.81 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| 比旋光度 | D25 +17 ±2.5° (c = 0.1 in ethanol) |
| 沸点 | 747.3±70.0 °C(Predicted) |
| 密度 | 2.17±0.1 g/cm3(Predicted) |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 13.05±0.70(Predicted) |
| 色 | 白色～淡黄色 |
| Merck | 13,4152 |
| BRN | 1225932 |
| 安定性 | -20°C の DMSO 溶液で最大 3 か月間保存できます。 |
| InChI | InChI=1/C10H12FN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6+,9-/s3 |
| InChIKey | HBUBKKRHXORPQB-VOSPVXAENA-N |
| SMILES | C12N=C(N=C(N)C=1N=CN2[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1)F |&1:10,11,13,15,r| |
| CAS データベース | 21679-14-1(CAS DataBase Reference) |
化学的特性
White Solid
安全性と法規制
| GHS 分類 | WarningH302 (95.5%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 44 reports by companies from 6 notifications to the ECHA C&L Inventory. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 4 (95.5%) |
| 処分方法 | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| 相互作用 | Fludarabine may raise the concentration of blood uric acid as part of a tumor lysis syndromedosage adjustment of antigout agents /allopurinol, colchicine, probenecid, sulfinpyrazone/ may be necessary to control hyperuricemia and goutallopurinol may be preferred to prevent or reverse fludarabine-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents.Leukopenic and/or thrombocytopenic effects of fludarabine may be increased with concurrent or recent therapy if these medications /blood dyscrasia causing medications/ cause the same effectsdosage adjustment of fludarabine, if necessary, should be based on blood counts.Additive bone marrow depression may occurdosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively.Concurrent use with fludarabine is not recommended because of a possible increased risk of fatal pulmonary toxicity. /Pentostatin/For more Interactions (Complete) data for FLUDARABINE (10 total), please visit the HSDB record page. |
| Hepatotoxicity | In clinical trials, serum enzymes elevations occurred in only a small proportion of patients treated with fludarabine for leukemia. The role of fludarabine as opposed to other antineoplastics used in antileukemic regimens was not always clear from these studies. Cases of clinically apparent liver injury due to fludarabine have been reported to occur, but few details were available and most patients were receiving other cancer chemotherapeutic agents. |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)fludarabineDILI NegativeOralDOI:10.1016/j.drudis.2019.09.022 |
| Non-Human Toxicity Excerpts | Dose-related adverse effects on the male reproductive system have been demonstrated in mice, rats, and dogseffects consisted of a decrease in mean testicular weights in mice and rats with a trend toward decreased testicular weights in dogs, and degeneration and necrosis of spermatogenic epithelium of the testes in mice, rats, and dogs.Studies in rats at intravenous doses of 0, 1, 10, or 30 mg per kg of body weight (mg/kg) per day on days 6 to 15 of gestation found an increased incidence of skeletal malformations. Studies in rabbits at doses of 5 and 8 mg/kg per day found dose-related teratogenic effects (external deformities and skeletal malformations). |
| Antidote and Emergency Treatment | Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/ |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| F | 10 |
| 水環境危害等級（WGK） | 3 |
| RTECS 番号 | AU6207000 |
| 税関コード | 29349990 |
| 危険文句（R） | 23/24/25-36/37/38-39/23/24/25-39-22 |
| 危険表示 | Xn |
| 安全措置（S） | 26-36/37-45-36 |
| 危険等級 | Muta. 2Repr. 2 |
| 貯蔵分類 | 11 - Combustible Solids |
| 有害物質データ | 21679-14-1(Hazardous Substances Data) |
用途
使用
Fludarabine is not one of the most used drugs in pediatric oncology area. It is used in combination with other drugs to treat AML in children, mostly those who are receiving second-line therapy. It is commonly sold as 10 mg film-coated tablets and IV vial containing 50mg.
一般的な説明
The drug is available as the phosphate salt in a 50-mg vialfor IV use. Fludarabine is used to treat chronic lymphocyticleukemia and non-Hodgkin’s lymphoma. The mechanism ofaction involves the triphosphate metabolite and its inhibitionof DNA chain elongation. The 2-fluoro group on the adeninering renders fludarabine resistant to breakdown byadenosine deaminase. The drug is rapidly dephosphorylatedto 2-fluoro-ara-adenosine (F-ara-A) after administration. Fara-A is taken into the cell and subsequently re-phosphorylatedto yield the triphosphate (F-ara-ATP), the active drugspecies. Resistance can occur via decreased expression ofthe activating enzymes and decreased drug transport.Fludarabine is orally bioavailable and is distributed throughoutthe body reaching high levels in liver, kidney, andspleen. The drug is metabolized to F-ara-A, which enterscells via the nucleoside transport system and is rephosphorylatedby deoxycytidine kinase to fludarabine monophosphateand finally fludarabine triphosphate, the activespecies. About 25% of F-ara-A is excreted unchanged inurine. Drug interactions include an increased incidence offatal pulmonary toxicity when fludarabine is used in combinationwith pentostatin. Additionally, fludarabine may potentiate the effects of several other anticancer drugs includingcytarabine, cyclophosphamide, and cisplatin.Toxicities include myelosuppression, immunosuppression,fever, nausea, and vomiting.