VINBLASTINE

VINBLASTINE 화학적 특성, 용도, 생산

• 개요

  An alkaloid derived from the periwinkle, Catharanthus roseus (formerly Vinca rosea) used as an antitumor drug in the treatment of Hodgkins lymphoma and other cancers. It binds to the microtubule subunit, tubulin, at a site distinct from that of colchicine and podophyllotoxin. This binding is reversible, temperature dependent and rapid, and results in large tubulin aggregates of highly ordered structure (vinblastine paracrystals).

• 물리적 성질

  Appearance: needlelike crystals were produced when recrystallized by methanol. Solubility: soluble in chloroform, acetone, and ethanol. Melting point: 211– 216?°C.?Sulfate melting point of vinblastine is 284–285?°C; hydrochloric acid melting point of vinblastine is 244–246?°C (decomposes). Specific optical rotation: +42°.

• 용도

  Vinblastine is used for severe lymphoblastic leukemia, Hodgkin’s disease, nonHodgkin’s lymphoma, neuroblastoma, sarcoma, and other cancerous diseases.

• Indications

  It was recorded in the Pharmacopoeia of the People’s Republic of China (2015), the British Pharmacopoeia (2017), the United States Pharmacopeia (40), the Japanese Pharmacopoeia (17th ed.), the European Pharmacopoeia (9th ed.), and The International Pharmacopoeia (5th ed.).
  Vinblastine sulfate injection is used as the first-line therapy to treat Hodgkin lymphoma, lymphocytic leukemia, testis tumor, and choriocarcinoma intravenously in clinical practice generally according to ABVD methods (Adriamycin, bleomycin, vinblastine, and dacarbazine).

• Mechanism of action

  Vinblastine suppresses cell growth during metaphase, affects amino acid metabolism, in particular at the level of including glutamine acid into the citric acid cycle and preventing it from transformation into urea, and it also inhibits protein and nucleic acid synthesis.

• Pharmacokinetics

  Leukopenia is the dose-limiting side effect, and dose reductions are warranted in patients with serum bilirubin levels greater than 3 mg/dL. The drug-related impact on erythrocyte and thrombocyte levels usually is insignificant. Like vincristine, it is administered as an IV bolus or infusion. The initial elimination half-life of 3.7 minutes is similar to vincristine, but the 24.8-hour terminal half-life is significantly shorter.

• Clinical Use

  In addition to the hematologic indications that it shares with vincristine, vinblastine sulfate has found utility in the treatment of advanced testicular carcinoma (often in combination with bleomycin), advanced mycosis fungoides, Kaposi's sarcoma, and histiocytosis X.

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