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Carboplatin


ACCESSION NB: DB00958 (APRD00466)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
An organoplatinum compound that possesses antineoplastic activity. [PubChem]

VOLUME OF DISTRIBUTION: 16 L

CATEGORIES:
Antineoplastic Agents Cross-Linking Reagents

INDICATION:
For the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimen consists of PARAPLATIN and cyclophosphamide.

PHARMACODYNAMICS:
Carboplatin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.

MECHANISM OF ACTION:
Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

PROTEIN BINDING:
Very low

TOXICITY:
Toxic by ingestion. May be create toxic effect through inhalation or skin contact. May cause reproductive defects. May act as a sensitizer. ORL-RAT LD50 343 mg kg-1; SCN-RAT LD50 72 mg kg-1; IPN-MUS LD50 118 mg kg-1

AFECTED ORGANISMS:
Humans and other mammals