出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/28 15:45:50」(JST)
| Systematic (IUPAC) name | |
|---|---|
| (S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy- 3,14-dioxo1H-pyrano[3’,4’:6,7]-indolizino[1,2-b]quinolin- |
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| Clinical data | |
| Trade names | Camptosar |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a608043 |
| Pregnancy cat. | D (Australia, United States) |
| Legal status | POM (UK), ℞-only (U.S.) |
| Routes | Intravenous |
| Pharmacokinetic data | |
| Bioavailability | NA |
| Metabolism | Hepatic glucuronidation |
| Half-life | 6 to 12 hours |
| Excretion | Biliary and renal |
| Identifiers | |
| CAS number | 100286-90-6 Y |
| ATC code | L01XX19 |
| PubChem | CID 60838 |
| DrugBank | DB00762 |
| ChemSpider | 54825 Y |
| UNII | 7673326042 Y |
| KEGG | D08086 Y |
| ChEMBL | CHEMBL481 Y |
| Chemical data | |
| Formula | C33H38N4O6 e |
| Mol. mass | 586.678 g/mol (Irinotecan) 623.139 g/mol (Irinotecan hydrochloride) |
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| Y (what is this?) (verify) |
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Irinotecan (Camptosar, Pfizer; Campto, Yakult Honsha) is a drug used for the treatment of cancer.
Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin.
Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. This includes the regimen FOLFIRI, which consists of infusional 5-fluorouracil, leucovorin, and irinotecan.
Irinotecan received accelerated approval by the U.S. Food and Drug Administration (FDA) in 1996[1] and full approval in 1998.[2] 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.
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
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. The patient may experience a period of neutropenia (a clinically significant decrease of neutrophils in the blood) while the bone marrow increases white cell production to compensate.
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 and often suffer from Gilbert's syndrome. During chemotherapy, they 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 neutropenia and diarrhea.[3]
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.[3]
In 2005, the FDA made changes to the labeling of irinotecan to add pharmacogenomics recommendations, such that irinotecan recipients with a homozygous (both of the two gene copies) polymorphism in UGT1A1 gene, to be specific, the *28 variant, should be considered for reduced drug doses.[4] Irinotecan is one of the first widely-used chemotherapy agents that is dosed according to the recipient's genotype.[5]
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| リンク元 | 「イリノテカン」 |
| 関連記事 | 「hydrochloride」 |