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Systematic (IUPAC) name


CAS number 100286-90-6 begin_of_the_skype_highlighting              100286-90-6      end_of_the_skype_highlighting
ATC code L01XX19
PubChem CID 3750
DrugBank APRD00579
Chemical data
Formula C33H38N4O6 
Mol. mass 586.678 g/mol
677.185 g/mol (hydrochloride)
Pharmacokinetic data
Bioavailability NA
Metabolism Hepatic glucuronidation
Half-life 6 to 12 hours
Excretion Biliary and renal
Therapeutic considerations
Pregnancy cat. D (Au, U.S.)
Legal status POM (UK), ℞-only (U.S.)
Routes Intravenous
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Irinotecan (Camptosar, Pfizer; Campto, Yakult Honsha) is a drug used for the treatment of cancer.

Irinotecan is a topoisomerase 1 inhibitor, which prevents DNA from unwinding. Chemically, it is a semisynthetic analogue of the natural alkaloid camptothecin.

Its main use is in colon cancer, particularly in combination with other chemotherapy agents. This includes the regimen FOLFIRI which consists of infusional 5-fluorouracil, leucovorin, and irinotecan.

Irinotecan was approved by the U.S. Food and Drug Administration (FDA) in 1994. During development, it was known as CPT-11.

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Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. This is then inactivated by glucuronidation by uridine diphosphate glucoronosyltransferase 1A1 (UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription.

Side effects

The most significant adverse effects of irinotecan are severe diarrhea and extreme suppression of the immune system.


Irinotecan-associated diarrhea is severe and clinically significant, sometimes leading to severe dehydration requiring hospitalization or intensive care unit admission. This side effect is managed with the aggressive use of antidiarrheals such as loperamide or Lomotil with the first loose bowel movement.


The immune system is adversely impacted by irinotecan. This is reflected in dramatically lowered white blood cell counts in the blood, in particular the neutrophils. While the bone marrow, where neutrophils are made, cranks up production to compensate, the patient may experience a period of neutropenia, that is, a clinical lack of neutrophils in the blood.


Irinotecan is converted by an enzyme into its active metabolite SN-38, which is in turn inactivated by the enzyme UGT1A1 by glucuronidation.

People with variants of the UGT1A1 called TA7, also known as the "*28 variant", express fewer UGT1A1 enzymes in their liver often suffering from Gilbert's syndrome. During chemotherapy, these patients effectively receive a larger than expected dose because their bodies are not able to clear irinotecan as fast as others. In studies this corresponds to higher incidences of severe diarrhea and neutropenia [1].

In 2004, a clinical study was performed that both validated prospectively the association of the *28 variant with greater toxicity and the ability of genetic testing in predicting that toxicity before chemotherapy administration.[1].

In 2005, the FDA made changes to the labelling of irinotecan to add pharmacogenomics recommendations that patients with polymorphisms in UGT1A1 gene, specifically the *28 variant, should perhaps receive reduced drug doses. Irinotecan is one of the first widely-used chemotherapy agents that is dosed for each patient according to his genotype[2].

See also

  • Camptothecin
  • Topotecan (Hycamtin)
  • Pharmacogenomics
  • NK012, a nanodevice formulation of SN-38 an irinotecan metabolite


  1. ^ a b Innocenti F, Undevia SD, Iyer L, et al. (April 2004). "Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan". J. Clin. Oncol. 22 (8): 1382–8. doi:10.1200/JCO.2004.07.173. PMID 15007088. 
  2. ^ O'Dwyer PJ, Catalano RB (October 2006). "Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy". J. Clin. Oncol. 24 (28): 4534–8. doi:10.1200/JCO.2006.07.3031. PMID 17008691. 

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