[4-[2-Amino-6-(cyclopropylamino)-9-purinyl]-1-cyclopent-2-enyl]methanol; sulfuric acid

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: [4-[2-Amino-6-(cyclopropylamino)-9-purinyl]-1-cyclopent-2-enyl]methanol; sulfuric acid
• 英文别名: [4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol;sulfuric acid
• 化学式: C14H20N6O5S
• 分子量: 384.41
• InChiKey: MBFKCGGQTYQTLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.44
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  185
• 氢给体数：
  5
• 氢受体数：
  10

ADMET

代谢

阿巴卡韦部分通过醇脱氢酶（形成5'-羧酸）和葡萄糖醛酸化（形成5'-葡萄糖醛酸苷）进行代谢。

Abacavir is partially metabolized by alcohol dehydrogenase (to form the 5'-carboxylic acid) and glucuronidation (to form the 5'-glucuronide).

来源:Hazardous Substances Data Bank (HSDB)

代谢

阿巴卡韦的代谢命运尚未完全确定，但该药物在肝脏中代谢。阿巴卡韦通过醇脱氢酶代谢形成5-羧酸，通过葡萄糖醛酸转移酶代谢形成5-葡萄糖苷酸；这些代谢物似乎没有抗病毒活性。细胞色素P450同工酶在阿巴卡韦代谢中的参与是有限的。

The metabolic fate of abacavir has not been fully determined, but the drug is metabolized in the liver. Abacavir is metabolized by alcohol dehydrogenase to form the 5-carboxylic acid and by glucuronyltransferase to form the 5-glucuronide; these metabolites do not appear to have any antiviral activity. Any involvement of cytochrome p450 isoenzymes in the metabolism of abacavir is limited.

来源:Hazardous Substances Data Bank (HSDB)

代谢

细胞内，阿巴卡韦通过腺苷酸转移酶磷酸化生成阿巴卡韦一磷酸盐；然后阿巴卡韦一磷酸盐在细胞质酶催化的反应中转化为卡波维一磷酸盐，接着通过细胞激酶转化为卡波维三磷酸盐。阿巴卡韦到卡波维三磷酸盐的细胞内（宿主细胞）转化是药物发挥抗病毒活性的必要条件。在CD4+ CEM细胞中，卡波维三磷酸盐的体外半衰期为3.3小时。

Intracellularly, abacavir is phosphorylated to abacavir monophosphate by adenosine phosphotransferase; abacavir monophosphate is then converted to carbovir monophosphate in a reaction catalyzed by cytosolic enzymes and then to carbovir triphosphate by cellular kinases. Intracellular (host cell) conversion of abacavir to carbovir triphosphate is necessary for the antiviral activity of the drug. The in vitro intracellular half-life of carbovir triphosphate in CD4+ CEM cells is 3.3 hours.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用乙醇与阿巴卡韦可能会导致阿巴卡韦的浓度和半衰期增加，这是由于酒精脱氢酶通过共同代谢途径竞争所致。

Concurrent use /of ethanol/ with abacavir may result in increased concentrations and half-life of abacavir as a result of competition for common metabolic pathways via alcohol dehydrogenase.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在接受口服美沙酮维持治疗的稳定患者中，开始使用600毫克每日两次的阿巴卡韦治疗，美沙酮的清除率增加了22％；在大多数患者中，清除率的增加在临床上不会显著；少数患者可能需要增加美沙酮的剂量。

Methadone clearance increased 22% in patients stabilized on oral methadone maintenance therapy who started abacavir therapy with 600 mg twice daily; increase in clearance will not be clinically significant in the majority of patients; methadone dosage increase may be required in a small number of patients.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要进行治疗……。监测休克，如有必要进行治疗……。预见并处理癫痫发作……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用生理盐水连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

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/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于无意识、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。监测心率和必要时治疗心律失常。 ... 开始静脉输液，使用D5W/SRP：“保持开放”，最低流量/。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象。用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和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/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

保持呼吸道通畅，必要时协助通气。如果出现昏迷、癫痫、低血压或过敏性反应，则进行治疗。通过静脉输液补充因胃肠炎导致的体液丢失。通过静脉输液维持稳定的尿流量，以缓解结晶尿并逆转肾功能不全。用适量的碳酸氢钠治疗乳酸酸中毒，并停用引起问题的药物。这些药物没有特定的解毒剂。给予活性炭。

Maintain an open airway and assist ventilation if needed. Treat coma, seizures, hypotension or anaphylaxis if they occur. replace fluid losses resulting from gastroenteritis with intravenous crystalloids. Maintain steady urine flow with intravenous fluids to alleviate crystalluria and reverse renal dysfunction. Treat lactic acidosis with judicious doses of sodium bicarbonate and by withdrawal of the offending drug. There are no specific antidotes for these agents. Administer activated charcoal.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在口服600毫克放射性阿巴卡韦后，82.2%的剂量通过尿液排出，16%的剂量通过粪便排出。尿液中的5-羧酸代谢物、5-葡萄糖苷酸代谢物和未改变的阿巴卡韦分别占回收放射性活性的30%、36%和1.2%；未识别的次要代谢物占尿液回收放射性活性的15%。

Following oral administration of a 600-mg dose of radiolabeled abacavir, 82.2% of the dose is excreted in urine and 16% of the dose is excreted in feces. The 5-carboxylic acid metabolite, 5-glucuronide metabolite, and unchanged abacavir accounted for 30, 36, and 1.2%, respectively, of recovered radioactivity in urine; unidentified minor metabolites accounted for 15% of recovered radioactivity in urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚不清楚阿巴卡韦是否分布到人乳中；该药物在大鼠乳汁中有分布。

It is not known whether abacavir is distributed into human milk; the drug is distributed into milk in rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Abacavir 在大鼠体内可通过胎盘。

Abacavir crosses the placenta in rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿巴卡韦的口服生物利用度很高，不受食物影响；脑脊液与血浆的药时曲线下面积（AUC）比率大约为0.3。

The oral bioavailability of abacavir is high with or without food; the CSF-to-plasma AUC ratio is approximately 0.3.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• Anti-viral and anti-tumor chemotherapy by administration of erythropoeitin
  申请人：——

  公开号：US20020052317A1

  公开（公告）日：2002-05-02

  The present invention provides methods using erythropoietin to improve the tolerance of anti-viral and anti-tumor chemotherapeutic regimens containing interferon. The invention also described improved methods to treat chronic HCV by adjusting the dose of ribavirin to tailor the active dose of the drug while supporting the hemoglobin levels in the patient with EPO. The present invention also provides anti-viral dosing regimens, particularly for chronic HCV comprising administration of an interferon containing anti-viral medicament, EPO, and a compound that reduces the amount of active tumor necrosis factor in the subject.

  本发明提供了使用促红细胞生成素改善含有干扰素的抗病毒和抗肿瘤化疗方案耐受性的方法。本发明还描述了治疗慢性 HCV 的改进方法，通过调整利巴韦林的剂量来定制药物的活性剂量，同时用 EPO 支持患者的血红蛋白水平。本发明还提供了抗病毒给药方案，特别是针对慢性HCV的抗病毒给药方案，包括服用含干扰素的抗病毒药物、EPO和一种可降低受试者体内活性肿瘤坏死因子量的化合物。
• Method of screening for drug hypersensitivity reaction
  申请人：——

  公开号：US20030096274A1

  公开（公告）日：2003-05-22

  Methods of assessing the risk of clinical signs of hypersensitivity reaction to nucleoside antiviral compounds, including abacavir, are described. The methods include genotyping subjects for polymorphisms in the TNF&agr; gene, the class 1 HLA genes, or a combination of both the TNF&agr; and HLA genes.

  本文介绍了评估核苷类抗病毒化合物（包括阿巴卡韦）超敏反应临床症状风险的方法。这些方法包括对受试者进行 TNF&agr; 基因、1 类 HLA 基因或 TNF&agr; 和 HLA 基因组合的多态性基因分型。
• CARBOCYCLIC NUCLEOSIDE HEMISULFATE AND ITS USE IN TREATING VIRAL INFECTIONS
  申请人：GLAXO GROUP LIMITED

  公开号：EP0983271B1

  公开（公告）日：2004-02-18
• IMPROVED ANTI-VIRAL AND ANTI-TUMOR CHEMOTHERAPY BY ADMINISTRATION OF ERYTHROPOEITIN
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1325324A1

  公开（公告）日：2003-07-09
• EP1325324A4
  申请人：——

  公开号：EP1325324A4

  公开（公告）日：2004-11-10