HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Fludarabin
2-fluoroadenine-9-β-d-arabinofuranoside · f-ara-a · Fludara · CS-1983 · Darabin · 2-F-ARAA · NSC 118218 · NSC-312887
Identifikatoren & physikalische Daten
| CAS No. | 21679-14-1 |
|---|---|
| Summenformel | C10H12FN5O4 |
| Durchschnittliche Molmasse | 285,23 g/mol |
| Monoisotopische Masse | 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 |
| Lokaler Name | Fludarabin |
Chemische & physikalische Eigenschaften
| XLogP | -0,6 |
|---|---|
| Polarare Oberfläche (TPSA) | 140 |
| H-Brücken-Donoren | 4 |
| H-Brücken-Akzeptoren | 9 |
| Frei drehbare Bindungen | 2 |
| Schwere Atome | 20 |
| Formalladung | 0 |
| Komplexität | 367 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agents |
| Color/Form | Crystals |
| Löslichkeit | Sparingly sol water, org solventsDMF: 20 mg/mL, clear, faintly yellowSoluble in DMF, DMSO, methanol or ethanol. Sparingly soluble in water |
| Human Drugs | Breast FeedingLactationMilk, HumanAntineoplastic AgentsCytotoxic medicines |
| Schmelzpunkt | 260 °C265-268°C |
| Collision Cross Section | 164.81 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Siedepunkt | 747.3±70.0 °C(Predicted) |
| Dichte | 2.17±0.1 g/cm3(Predicted) |
| Lagerbedingungen | 2-8°C |
| Aggregatzustand | Powder |
| pKa (Säurekonstante) | 13.05±0.70(Predicted) |
| Farbe | White to Pale Yellow |
| Merck | 13,4152 |
| BRN | 1225932 |
| Stabilität | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| 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 Datenbank | 21679-14-1(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | 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%) |
| Entsorgungsverfahren | 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. |
| Wechselwirkungen | 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 |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 29349990 |
| RTECS-Nr. | AU6207000 |
| R-Sätze (R) | 23/24/25-36/37/38-39/23/24/25-39-22 |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 26-36/37-45-36 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 21679-14-1(Hazardous Substances Data) |
| Gefahrenklasse | Muta. 2Repr. 2 |
Anwendungen & Verwendung
Verwenden
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.