カペシタビン 化学特性,用途語,生産方法
外観
白色～ほとんど白色、結晶性粉末～粉末又は塊
溶解性
ベンジルアルコール及びエタノール(99.5)に溶けやすく、水にやや溶けにくい。
用途
生体内で 5- フルオロウラシ
ルへと代謝されて DNA 合成阻害作用を示し
ます。
用途
カペシタビン（Capecitabine）とは、フッ化ピリミジン系代謝拮抗剤に類する抗悪性腫瘍剤（抗がん剤）。
フッ化ピリミジン系抗悪性腫瘍剤の代表ともいえるフルオロウラシル（5-FU）は、これまで乳癌や消化器癌の治療に最も多く使われてきた抗がん剤の一つであるが、カペシタビンは、骨髄細胞や消化管では活性体になりにくく腫瘍組織内でより選択的に5-FUを生成することを目的として、日本ロシュ研究所（現中外製薬株式会社鎌倉研究所）で創製された。
効能
抗悪性腫瘍薬, 代謝拮抗薬
商品名
カペシタビン (ダイト); カペシタビン (日医工); カペシタビン (東和薬品); ゼローダ (中外製薬)
使用上の注意
不活性ガス封入
説明
Capecitabine is a new oral fluoropyrimidine carbamate for patients with
advanced neoplastic disease, approved as Xeloda for the treatment of refractory
metastatic breast cancer after failure on Paclitaxel and an anthracycline-based
chemotherapy regimen ; it is a prodrug of doxifluridine (5-fluorouracil ; 5-FU)
activated by a cascade of 3 enzymes concentrated in human liver and cancer
tissue, resulting in the selective release of 5-FU at the tumor site and offering a
prolonged tumour exposure to 5-FU. Oral Capecitabine passes intact through
the intestinal mucosa, is converted first by carboxylesterase to 5'-deoxy-5-
fluorocytidine in the liver, then by cytidine deaminase to 5'-deoxy-5-fluorouridine
in the liver and tumour tissues and finally by thymidine phosphorylase to 5-FU in
tumors. Therefore, Xeloda is much safer and more effective than 5-FU (for
example, in the HCT116 human colon cancer and the MX-1 breast cancer
xenograft .models).
化学的特性
Colourless solid
使用
Capecitabine is an antineoplastic agent. Capecitabine is a prodrug of Doxifluridine (D556750).
定義
ChEBI: A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted to its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agen
used in the treatment of cancers.
一般的な説明
The drug is available in a 150- and 500-mg tablets for oraluse. This drug is a fluoropyrimidine carbamate prodrugform of 5-fluorouracil (5-FU). It is used to treat breast cancerand colorectal cancer. The drug is converted to 5-FU bythe enzyme thymidine phosphorylase following esterase activity to hydrolyze the carbamate moiety and deamination.Capecitabine is readily absorbed by the GI tract, and peakplasma levels of 5-FU occur about 2 hours after oral administration.Indications, drug interactions, and toxicities areequivalent to those of 5-FU.
臨床応用
Capecitabine is indicated for use as first-line therapy in patients with colorectal cancer. It also is used alone or in combination with docetaxel in patients with metastatic breast cancer who have experienced disease progression or recurrence after anthracycline therapy. Given b.i.d. in tablet form, the total daily dose is calculated based on patient body surface area and is taken 30 minutes after eating to avoid food-induced decreases in absorption. In addition to bone marrow suppression, nausea, and vomiting, the drug can induce severe diarrhea and a potentially disabling disorder termed “hand-and-foot syndrome” (palmar-plantar erythrodysethesia). Capecitabine inhibits CYP2C9 and, along with competition for serum protein binding sites, results in clinically significant drug–drug interactions with both warfarin and phenytoin.
代謝
Although capecitabine is a carbamylated analogue of cytidine , the drug actually is another 5-fluoro-dUMP prodrug. Given orally, it is extensively metabolized to fluorouracil, which is then converted to the active fluorinated deoxyribonucleotide as previously described. Thymidine phosphorylase, an enzyme involved in this biotransformation, is much more active in tumors than in normal tissue, which improves the tumor-selective generation of fluorouracil. Levels of active drug in the tumor can be up to 3.5-fold higher than in surrounding tissue, leading to a lower incidence of side effects compared to fluorouracil therapy. Because capecitabine is biotransformed to fluorouracil, it follows the same catabolic and elimination pathways reported for 5-fluorouracil.
カペシタビン 上流と下流の製品情報
原材料
準備製品