出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/25 14:06:09」(JST)
| IUPAC命名法による物質名 | |
|---|---|
| (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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| 臨床データ | |
| 胎児危険度分類 |
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| 法的規制 |
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| 投与方法 | 点滴静脈注射 |
| 薬物動態的データ | |
| 生物学的利用能 | NA |
| 代謝 | 肝臓、グルクロン酸化 |
| 半減期 | 6 ～ 12 時間 |
| 排泄 | 胆汁、腎臓 |
| 識別 | |
| CAS番号 | 100286-90-6 |
| ATCコード | L01XX19 |
| PubChem | CID 3750 |
| DrugBank | APRD00579 |
| KEGG | D08086 |
| 化学的データ | |
| 化学式 | C33H38N4O6 |
| 分子量 | 586.678 g/mol 677.185 g/mol (塩酸塩) |
イリノテカン (irinotecan) は、肺癌や転移性大腸癌などに使用される。カンレンボク由来の抗腫瘍性アルカロイドであるカンプトテシンから合成された抗悪性腫瘍薬である。トポイソメラーゼI阻害作用を有する。
塩酸塩として、ヤクルト本社よりカンプト注、第一三共よりトポテシンの商品名で製造販売されている。
イリノテカンはSN-38に加水分解されて活性化され、トポイソメラーゼⅠを阻害する。この時、ウリジン2リン酸グルクロン酸転移酵素1A1(UGT1A1)によって不活性化される。
日本において厚生労働省に認可された保険適応疾患は以下の通り。
小細胞肺癌、非小細胞肺癌、子宮頚癌、卵巣癌、有棘細胞癌、悪性リンパ腫（非ホジキンリンパ腫）、胃癌、大腸癌、乳癌
上記の他にも食道癌等においての効果も報告されてきている。
激しい下痢、吐き気が特徴的な副作用であり、そのほか骨髄抑制や、それによる白血球の減少等の副作用をきたす。
| 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- |
|
| Clinical data | |
| Trade names | Camptosar |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a608043 |
| Pregnancy category |
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| Legal status |
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| Routes of administration |
Intravenous |
| Pharmacokinetic data | |
| Bioavailability | NA |
| Metabolism | Hepatic glucuronidation |
| Biological half-life | 6 to 12 hours |
| Excretion | Biliary and renal |
| Identifiers | |
| CAS Registry Number | 100286-90-6 Y |
| ATC code | L01XX19 |
| PubChem | CID: 60838 |
| IUPHAR/BPS | 6823 |
| DrugBank | DB00762 Y |
| ChemSpider | 54825 Y |
| UNII | 7673326042 Y |
| KEGG | D08086 Y |
| ChEMBL | CHEMBL481 Y |
| Chemical data | |
| Formula | C33H38N4O6 |
| Molecular mass | 586.678 g/mol (Irinotecan) 623.139 g/mol (Irinotecan hydrochloride) |
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| Y (what is this?) (verify) | |
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.[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[2] and full approval in 1998.[3] During development, it was known as CPT-11.
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 co-phenotrope 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.[4]
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.[4]
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.[5] Irinotecan is one of the first widely used chemotherapy agents that is dosed according to the recipient's genotype.[6]
Recently it was shown that antitumor activity of irinotecan against glioblastoma can be enhanced by co-treatment with statins.[7] Similarly, it was shown that berberine may enhance chemosensitivity to irinotecan in colon cancer cells.[8]
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| リンク元 | 「ジルベール症候群」「イリノテカン」「irinotecan hydrochloride」 |
| 関連記事 | 「C」「CP」 |
| 体質性黄疸 | 遺伝形式* | ビリルビン型 | ビリルビン値 | 予後 |
| Crigler-Najjar症候群I型 | 常染色体劣性 | 間接型(非抱合) | 21-31mg/dl | 致死的 |
| Crigler-Najjar症候群II型 | 常染色体劣性 | 8-18mg/dl | 良好 | |
| Gilbert症候群 | 常染色体優性 | <6mg/dl | きわめて良好 | |
| Dubin-Johnson症候群 | 常染色体劣性 | 直接型(抱合) | 2-5(-25)mg/dl | きわめて良好 |
| Rotor症候群 | 常染色体劣性 | 2-5(-20)mg/dl | きわめて良好 | |
| *劣性か優性かについては例外あり | ||||