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Plicamycin


ACCESSION NB: DB06810


TYPE: small molecule


GROUP: approved, withdrawn


DESCRIPTION:
Plicamycin is an antineoplastic antibiotic produced by Streptomyces plicatus. It has been used in the treatment of testicular cancer, Paget’s disease of bone, and, rarely, the management of hypercalcemia. The manufacturer discontinued plicamycin in 2000.

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Antibiotics, Antineoplastic

ABSORPTION: Not Available

INDICATION:
For the treatment of testicular cancer, as well as hypercalcemia and hypercalciuria associated with a variety of advanced forms of cancer.

PHARMACODYNAMICS:
Plicamycin is lethal to Hela cells in 48 hours at concentrations as low as 0.5 micrograms per milliliter of tissue culture medium. Plicamycin has shown significant anti-tumor activity against experimental leukemia in mice when administered intraperitoneally.

MECHANISM OF ACTION:
Plicamycin is presumed to inhibit cellular and enzymic RNA synthesis by forming a complex with DNA. Plicamycin may also lower calcium serum levels by inhibiting the effect of parathyroid hormone upon osteoclasts or by blocking the hypercalcemic action of pharmacologic doses of vitamin D.

PROTEIN BINDING:
There is no evidence of protein binding, nor is there any evidence of metabolism of the carbohydrate moiety of the drug to carbon dioxide and water with loss through respiration.

TOXICITY:
The most important form of toxicity associated with the use of plicamycin consists of a dose-related bleeding syndrome which usually begins with an episode of epistaxis. Plicamycin crosses the blood-brain barrier; the concentration found in brain tissue is low but it persists longer than in other tissues.

AFECTED ORGANISMS:
Not Available