Introduction
Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)
Uses
Vinblastine is a vinca alkaloid used to treat breast cancer, testicular cancer, neuroblastoma, Hodgkin's and non-Hodgkins lymphoma, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.
For treatment of breast cancer, testicular cancer, lymphomas, neuroblastoma, Hodgkin's and non-Hodgkin's lymphomas, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.
Associated Conditions
Pharmacodynamics
Vinblastine is a vinca alkaloid antineoplastic agent. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units: vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
Mechanism of Action
The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.
Protein Binding
98-99%
Route of Elimination
The major route of excretion may be through the biliary system.
Half Life
Triphasic: 35 min, 53 min, and 19 hours
Toxicity
Oral, mouse: LD50 = 423 mg/kg; Oral, rat: LD50 = 305 mg/kg.
Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of vinblastine.
- Exercise caution with St. John's Wort. This herb induces CYP3A metabolism, which may reduce serum levels of vinblastine.
Dosage
Child (Intravenous): Initial 2.5 mg/m2 of BSA, increased dose at wkly intervals in increments of about 1.25 mg/m2 until leukocyte count decreases to about 3000/ mm3, or max wkly dose of 12.5 mg/m2 reached. Do not increase dose once leukocyte count reaches approximately 3000 cells/mm3, instead, a dose of 1 increment smaller to be admin at wkly intervals for maintenance i.e. patient receives the max dose that does not cause leucopenia. If onolytic activity is encountered before leucopenic effect, then there is no need to increase subsequent doses. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm3. Duration of maintenance therapy depends on disease state and the antineoplastic agent combination.