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Camptothecin

Camptothecin. Conni Covington Seboo Dhakhwa. What is Camptothecin?. Camptothecin is an alkaloid produced by Camptotheca acuminata and Mappia foetida Irinotecan is a less toxic, more water-soluble derivative of camptothecin

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Camptothecin

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  1. Camptothecin Conni Covington Seboo Dhakhwa

  2. What is Camptothecin? • Camptothecin is an alkaloid produced by Camptotheca acuminata and Mappia foetida • Irinotecan is a less toxic, more water-soluble derivative of camptothecin • Irinotecan is sold under the name Camptosar® by Pharmacia & Upjohn.

  3. Indications • First-line treatment of metastatic cancers of the colon and rectum • Treatment of cancers of the colon and rectum that have progressed following treatment with 5FU/LV

  4. Unlabeled Uses • Cancers of the lung, cervix, pancreas, breast, and stomach; leukemia, lymphoma

  5. Contraindications: Pregnancy (category D) Breastfeeding Neutropenic fever (discontinue) Precautions: Hepatic dysfunction (adjust dose) Hyperbilirubinemia Contraindications and Precautions

  6. Metabolism • Primary route by P450s –inactive metabolite • Minor route by carboxyesterases – active metabolite SN-38 • Minor route inhibition can lead to buildup of toxic SN-38

  7. Adverse Reactions • Alopecia • Diarrhea • Vomiting • Weakness • Neutropenia • Fever • Stomach pain and cramping • Dyspnea

  8. Dosage schedule • May be every week or every three weeks, according to administered dose • Varies according to single treatment or combination treatment • May require adjustment based on severity of side effects

  9. Topoisomerase I • Binds to DNA molecule beyond the replication fork • Cleaves a phosphodiester bond on one strand of DNA and binds to the cleaved site • Reduces torsional strain on the molecule during replication • May be involved in RNA transcription

  10. Inhibition of Topo I by camptothecin • Camptothecin stabilizes the cleavable complex so that the nick in the DNA is not religated • When the replication fork reaches the camptothecin-bound complex, it results in a replication-halting double-strand break • Specific to S-phase of the cell cycle

  11. References • Lexi-Comp online • Clinical Pharmacology Online • Liu, Leroy F. Annu. Rev. Biochem, 1989. 58: 351-375 • Herben, Virginie M.M. et al. Pharm. World Sci. 1998;20(4): 161-172

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