ゲムシタビン 化学特性,用途語,生産方法
外観
白色～うすい黄色、結晶性粉末～粉末
用途
ゲムシタビン（Gemcitabine、略号：GEM）とは、抗癌剤として用いられる含フッ素ヌクレオシドの一種である。
効能
抗悪性腫瘍薬, 代謝拮抗薬
使用上の注意
アルゴン封入
説明
Gemcitabine is an anticancer nucleoside analog that inhibits the growth of HL-60 promyelocytic leukemia cells with an LC
50 value of 40 nM. It inhibits the growth of MX-1 mammary, CX-1, HC-1, GC3, and VRC5 colon, LX-1, Calu-6, and NCI-H460 lung, and HS766T, PaCa-2, PANC-1, and BxPC-3 pancreatic cancer tumors in mouse xenograft models (45-93% inhibition). Gemcitabine is a prodrug that is metabolized to a diphosphate and triphosphate form in cells. The triphosphate form is incorporated into DNA which induces masked chain termination and cell death. By specifically inhibiting growth arrest and DNA damage inducible protein 45 a (Gadd45a), a key mediator of active DNA demethylation, gemcitabine, at concentrations ranging from 34 to 134 nM, inhibits repair-mediated DNA demethylation in a methylation-sensitive reporter assay. Gemcitabine also has broad antiretroviral activity, decreasing MuLV cell infectivity, a murine AIDS model, in cell culture (EC
50 = ~1.5 nM) and inhibits the progression of murine AIDS
in vivo at a dose of 1-2 mg/kg per day.
使用
Gemcitabine(Gemzar) belongs to the group of medicines called antimetabolites. It is used alone or in combination with other medicines to treat cancer of the breast, ovary, pancreas, and lung. Gemcitabine interferes with the growth of cancer cells, which a
適応症
Gemcitabine (Gemzar), an antimetabolite, undergoes
metabolic activation to difluorodeoxycytidine triphosphate,
which interferes with DNA synthesis and repair.
It is the single most active agent for the treatment of
metastatic pancreatic cancer, and it is used as a first-line
treatment for both pancreatic and small cell lung cancer.
It is administered by intravenous infusion. The
dose-limiting toxicity is bone marrow suppression.
一般的な説明
The drug is available as the hydrochloride salt in 200- and1,000-mg lyophilized single-dose vials for IV use.Gemcitabine is used to treat bladder cancer, breast cancer,pancreatic cancer, and NSCLC. Gemcitabine is a potent radiosensitizer,and it increases the cytotoxicity of cisplatin.The mechanism of action of this fluorine-substituted deoxycytidineanalog involves inhibition of DNA synthesis andfunction via DNA chain termination. The triphosphatemetabolite is incorporated into DNA inhibiting severalDNA polymerases and incorporated into RNA inhibitingproper function of mRNA. Resistance can occur because ofdecreased expression of the activation enzyme deoxycytidinekinase or decreased drug transport as well as increasedexpression of catabolic enzymes. Drug oral bioavailabilityis low because of deamination within the GI tract, and thedrug does not cross the blood-brain barrier. Metabolism bydeamination to 2', 2'-difluorouridine (dFdU) is extensive.Drug toxicity includes myelosuppression, fever, malaise,chills, headache, myalgias, nausea, and vomiting.
危険性
Human systemic effects
作用機序
Gemcitabine shows
good activity against human leukemic cell lines,
a number of murine solid tumors, and human
tumor xenografts. Gemcitabine was
significantly more cytotoxic than cytarabine in
Chinese hamster ovary cells. The major cellular
metabolite is the 5'-triphosphate of gemcitabine.
The cytotoxicity was competitively reversed by
deoxycytidine, suggesting that the biological
activity required phosphorylation by deoxycytidine kinase. Tumor-bearing mice were treated with either gemcitabine or cytarabine (20 mg/kg). DNA
synthesis reached 1 % of control levels upon
administration of gemcitabine. The greater
accumulation of gemcitabine-5'-triphosphate
compared with cytarabine-5'-triphosphate may
cause greater cytotoxicity and therapeutic activity. Further gemcitabine may enhance its own cytotoxic effects by self-potentiation mechanisms that act on, e. g., deoxycytidine monophosphate
deaminase, deoxycytidine kinase or on DNA synthesis.
ゲムシタビン 上流と下流の製品情報
原材料
準備製品