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 Vincristine sulfate

vincristine sulfate is the sulfate salt of a natural alkaloid isolated from the plant Vinca rosea Linn with antimitotic and antineoplastic activities. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Applications

Vincristine is delivered via intravenous infusion for use in various types of chemotherapy regimens. Its main uses are in non-Hodgkin's lymphoma as part of the chemotherapy regimen CHOP, Hodgkin's lymphoma as part of MOPP, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen, in acute lymphoblastic leukemia, and in treatment for nephroblastoma (Wilms tumor, a kidney tumor common in children). It is also used to induce remission in ALL with Dexamethasone and L Asparaginase. Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP). It is used in combination with prednisone to treat childhood leukemia.  From http://en.wikipedia.org/wiki/Vincristine.

DRUG DESCRIPTION

VINCASAR PFS® (vincristine sulfate injection, USP) is the salt of an alkaloid obtained from a common flowering herb, the periwinkle plant (Vinca rosea Linn.). Originally known as leurocristine, it has also been referred to as LCR and VCR. Vincristine sulfate is a white to slightly yellow, amorphous powder. It is soluble in methanol, freely soluble in water, but only slightly soluble in 95% ethanol. In 98% ethanol, vincristine sulfate has an ultraviolet spectrum with maxima at 221 nm (e+ 47,100). VINCASAR PFS®, a sterile, preservative-free, single use only solution, is available in 1 mg (1 mg/1 mL) and 2 mg (2 mg/2 mL) vials. Each mL contains vincristine sulfate, 1 mg (1.08 mmoL); mannitol, 100 mg; water for injection, q.s. Acetic acid and sodium acetate have been added for pH control. The pH of VINCASAR PFS ranges from 3.5 to 5.5. This product is a sterile solution for cancer/oncolytic use.

CLINICAL PHARMACOLOGY

The mechanisms of action of vincristine sulfate remain under investigation.1 The mechanism of action of vincristine sulfate has been related to the inhibition of microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Central-nervous-system leukemia has been reported in patients undergoing otherwise successful therapy with vincristine sulfate. This suggests that vincristine sulfate does not penetrate well into the cerebrospinal fluid. Pharmacokinetic studies in patients with cancer have shown a triphasic serum decay pattern following rapid intravenous injection. The initial, middle, and terminal half-lives are 5 minutes, 2.3 hours, and 85 hours respectively; however, the range of the terminal half-life in humans is from 19 to 155 hours. The liver is the major excretory organ in humans and animals; about 80% of an injected dose of vincristine sulfate appears in the feces and 10% to 20% can be found in the urine. Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound.2 Current principles of cancer chemotherapy involve the simultaneous use of several agents. Generally, each agent used has a unique toxicity and mechanism of action so that therapeutic enhancement occurs without additive toxicity. It is rarely possible to achieve equally good results with single-agent methods of treatment. Thus, vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone-marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy).

History

Having been used as a folk remedy for centuries, studies in the 1950s revealed that C. roseus contained 70 alkaloids, many of which are biologically active. While initial studies for its use in diabetes mellitus were disappointing, the discovery that it caused myelosuppression (decreased activity of the bone marrow) led to its study in mice with leukemia, whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skelly-B defatting agent and an acid benzene extract led to a fraction termed "fraction A". This fraction was further treated with aluminium oxide, chromatography, trichloromethane, benz-dichloromethane and separation by pH to yield vincristine. Vincristine was approved by the United States Food and Drug Administration (FDA) in July 1963 as Oncovin. The drug was initially discovered by a team lead by Dr. J.G. Armstrong; it was then marketed by Eli Lilly and Company. From http://en.wikipedia.org/wiki/Vincristine.

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