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Vincristine Sulfate Injection

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Vincristine Sulfate Injection

CLINICAL PHARMACOLOGY

The mechanisms of action of vincristine sulfate remain under investigation. The mechanism of action of vincristine sulfate has been related to the inhibition of microtubule formation in 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 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. The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes (see PRECAUTIONS). 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.

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). See DOSAGE AND ADMINISTRATION section for possible increased toxicity when used in combination therapy.

Last reviewed on RxList: 9/16/2008
This monograph has been modified to include the generic and brand name in many instances.

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