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Vincristine Sulfate

Generic: Vincristine
Common Name: Leurocristine, Vinca alkaloid Brands: Oncovin, Marqibo

Medicinal Chemistry

Molecular Weight 923.04
Molecular Formula C46H56N4O10.H2SO4
IUPAC Name
Methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(1S,3S,5S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-1,4,5,6,7,8,9,10-octahydro-2H-3,7-methanoazacycloundecino[5,4-b]indol-9-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate sulfate

Pharmacognosy

Biological Source

Catharanthus roseus (Madagascar Periwinkle)

Active Constituents

Vincristine, Vinblastine

Pharmacology & Synthesis

Mechanism of Action

Binds specifically to tubulin, inhibiting assembly of microtubules and arresting cells in metaphase.

Pharmacokinetics (ADME)

A: Administered IV only (fatal if given intrathecally).
D: Extensive tissue binding, poor BBB penetration.
M: Hepatic via CYP3A4.
E: Biliary and fecal.

Pharmacodynamics

Cytotoxic to rapidly dividing cells; highly effective in acute lymphoblastic leukemia (ALL).

Synthesis Pathway

Dimeric alkaloid formed naturally (N-methyl group of vindoline moiety replaced by an N-formyl group).

Safety, Warnings & Interactions

Adverse Effects

Peripheral neuropathy (dose-limiting), severe constipation, paralytic ileus, alopecia.

Contraindications

Charcot-Marie-Tooth syndrome, severe demyelinating conditions, intrathecal administration.

Drug Interactions

CYP3A4 inhibitors (itraconazole) increase severe neurotoxicity.

Pharmaceutics & Compendia

Dosage Forms Injection (as Vincristine Sulfate)
Official Compendia IP, BP, USP
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