出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/03 17:49:03」(JST)
| IUPAC命名法による物質名 | |
|---|---|
| cis-Diammine(1,1-cyclobutanedicarboxylato)-platinum(II) | |
| 臨床データ | |
| 胎児危険度分類 | - |
| 法的規制 | 毒薬、指定医薬品、処方せん医薬品 |
| 投与方法 | 点滴静注 |
| 薬物動態的データ | |
| 生物学的利用能 | - |
| 血漿タンパク結合 | 非常に低い |
| 代謝 | - |
| 半減期 | α相:0.16～0.32時間 β相:1.29～1.69時間 |
| 排泄 | 尿中 |
| 識別 | |
| CAS登録番号 | 41575-94-4 |
| ATCコード | L01XA02 |
| PubChem | CID 498142 |
| KEGG | D01363 |
| 化学的データ | |
| 化学式 | C6H12N2O4Pt |
| 分子量 | 371.249 |
カルボプラチン（Carboplatin : CBDCA）とは、シスプラチンの抗腫瘍活性を弱めることなく、腎毒性および嘔気・嘔吐などの副作用を軽減することを目的にJohnson Matthey社が合成し、英国の癌研究所、米国の国立癌研究所（NCI）、米国のブリストル・マイヤーズ スクイブ社が開発した抗悪性腫瘍剤（抗がん剤）。
商品名は、パラプラチン（ブリストル・マイヤーズ）、後発医薬品として、カルボプラチン（沢井製薬など）、カルボメルク（マイラン製薬など）。
カルボプラチンはシスプラチンと同じ白金錯体であるが、シスプラチンに比べて腎毒性が低く、シスプラチン投与時には必要な水分負荷がカルボプラチン投与時には必要ない。またシスプラチンの特徴的な副作用である嘔気・嘔吐もカルボプラチンでは軽減されている。
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1,1-シクロブタンジカルボン酸配位子の一方がOH2に変換されることにより活性化され、DNAと反応、結合し、次いで、一方が外れた1,1-シクロブタンジカルボン酸基は不安定となり脱離し、その脱離部が同様に活性化され、更にDNAと結合して反応が終了する。DNAへの結合部位はシスプラチンと同様で、DNAの構成塩基であるグアニン、アデニンのN-7位に結合する。
骨髄抑制、ショック、アナフィラキシー様症状、間質性肺炎、急性腎不全、ファンコニー症候群、肝不全、肝機能障害、黄疸、消化管壊死、消化管穿孔、消化管出血、消化管潰瘍、出血性腸炎、偽膜性大腸炎、麻痺性イレウス、脳梗塞、血栓・塞栓症、心筋梗塞、うっ血性心不全、溶血性尿毒症症候群、急性呼吸窮迫症候群、播種性血管内凝固症候群、急性膵炎、悪心・嘔吐、食欲不振、下痢、口内炎、腹痛、便秘血尿、蛋白尿、蕁麻疹、発疹、末しょう神経障害（しびれ等）、頭痛、ALT (GPT) 上昇、AST (GOT) 上昇、Al-P上昇、ビリルビン上昇、LDH上昇、γ-GTP上昇、電解質代謝異常、脱毛、全身倦怠感、無力症、尿酸上昇、悪寒、脱水、体重減少、アルブミン低下、呼吸困難 、発熱、浮腫など。
また、類薬シスプラチンで聴力低下､難聴､耳鳴、うっ血乳頭､球後視神経炎､皮質盲溶血性貧血が生じることがある。
| Systematic (IUPAC) name | |
|---|---|
| cis-diammine(cyclobutane-1,1-dicarboxylate-O,O')platinum(II) | |
| Clinical data | |
| Trade names | Paraplatin |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a695017 |
| Pregnancy cat. | D (US) |
| Legal status | Rx Only |
| Routes | Intravenous |
| Pharmacokinetic data | |
| Bioavailability | complete |
| Protein binding | Very low |
| Half-life | 1.1-2 hours |
| Excretion | renal |
| Identifiers | |
| CAS number | 41575-94-4 Y |
| ATC code | L01XA02 |
| PubChem | CID 498142 |
| DrugBank | DB00958 |
| ChemSpider | 8514637 Y |
| UNII | BG3F62OND5 Y |
| KEGG | D01363 Y |
| ChEBI | CHEBI:31355 Y |
| ChEMBL | CHEMBL288376 N |
| Chemical data | |
| Formula | C6H12N2O4Pt |
| Mol. mass | 371.249 g/mol |
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Carboplatin, or cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II) (trade names Paraplatin and Paraplatin-AQ) is a chemotherapy drug used against some forms of cancer (mainly ovarian carcinoma, lung, head and neck cancers).[1] It was introduced in the late 1980s and has since gained popularity in clinical treatment due to its vastly reduced side-effects compared to its parent compound cisplatin. Cisplatin and carboplatin belong to the group of platinum-based antineoplastic agents, and interact with DNA to interfere with DNA repair.
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Carboplatin was discovered at Michigan State University[2], and developed at the Institute of Cancer Research in London. Bristol-Myers Squibb gained Food and Drug Administration (FDA) approval for carboplatin, under the brand name Paraplatin, in March 1989. Starting in October 2004, generic versions of the drug became available.
In terms of its structure, carboplatin differs from cisplatin in that it has a bidentate dicarboxylate (CBDCA) ligand in place of the two chloride ligand, which are the leaving groups in cisplatin. It exhibits lower reactivity and slower DNA binding kinetics, although it forms the same reaction products in vitro at equivalent doses with cisplatin. Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin cause different morphological changes in MCF-7 cell lines while exerting their cytotoxic behaviour [3]. The diminished reactivity limits protein-carboplatin complexes, which are excreted. The lower excretion rate of carboplatin means that more is retained in the body, and hence its effects are longer lasting (a retention half-life of 30 hours for carboplatin, compared to 1.5-3.6 hours in the case of cisplatin).
Two theories exist to explain the molecular mechanism of action of carboplatin with DNA:
The former is more accepted owing to the similarity of the leaving groups with its predecessor cisplatin, while the latter hypothesis envisages a biological activation mechanism to release the active Pt2+ species.
Relative to cisplatin, the greatest benefit of carboplatin is its reduced side effects, particularly the elimination of nephrotoxic effects. Nausea and vomiting are less severe and more easily controlled.
The main drawback of carboplatin is its myelosuppressive effect. This causes the blood cell and platelet output of bone marrow in the body to decrease quite dramatically, sometimes as low as 10% of its usual production levels. The nadir of this myelosuppression usually occurs 21–28 days after the first treatment, after which the blood cell and platelet levels in the blood begin to stabilize, often coming close to its pre-carboplatin levels. This decrease in white blood cells (neutropenia) can cause complications, and is sometimes treated with drugs like filgrastim. The most notable complication of neutropenia is increased probability of infection by opportunistic organisms, which necessitates readmission to hospital and treatment with antibiotics.
Carboplatin is less potent than cisplatin; depending on the strain of cancer, carboplatin may only be 1/8 to 1/45 as effective. The clinical standard of dosage of carboplatin is usually a 4:1 ratio compared to cisplatin; that is, for a dose that usually requires a particular dose of cisplatin, four times more carboplatin is needed to achieve the same effectiveness. The stable property of carboplatin is a mixed blessing: once uptake of the drug occurs, its retention half-life is considerably longer than cisplatin, but it is also this inertness that causes carboplatin to go right through the human body, and up to 90% of the carboplatin given can be recovered in urine.
The effectiveness of carboplatin can be increased by first incubating carboplatin in a sodium chloride (NaCl) solution. After 24 hours, an analysis is performed on the solution by separating the compounds by thin-layer chromatography (TLC). The TLC isolates cisplatin, carboplatin, and several platinum by-products in the solution. Numerous trials have shown a trend that the survival rate of E. coli dropped dramatically as the molarity of the NaCl incubating solution increased. The treated E. coli also showed decreased amounts of alkaline phosphatase, a protein indicator of cellular size. This suggests that as this incubated carboplatin solution is administered to cells, they began to shrink and eventually die; apparently by the same mechanism that cisplatin works.
GemCarbo chemotherapy (consisting of gemcitabine, also known as Gemzar, and carboplatin) is used to treat several different types of cancer, but is most commonly used to treat lung cancer.[4] GemCarbo chemotherapy is usually conducted as a day patient treatment, involving a blood test the day before. The drugs are administered by infusion. The GemCarbo regimen is given as a 21-day cycle. On the first day of treatment the patient is given both the gemcitabine and carboplatin. On the same day of the following week (day eight) there is a drip of gemcitabine only. There then follows a rest period of two weeks which completes one cycle of chemotherapy. The next cycle of treatment is given after a rest period, ends three weeks after the first injection. Usually 4–6 cycles of treatment are given over a period of 3–4 months to complete a full course of treatment. This treatment may prevent the further spread of the cancer or in some cases may reduce the size of the tumor between 20%-80%, depending upon the individual.
A recent study in mutant mice suggests that in the subset of women with breast cancer due to BRCA1 and BRCA2 genes (these cause a variety of familial breast cancer) carboplatin may be as much as 20 times more effective than the usual breast cancer treatments.[5] However, similar data in humans has not yet been shown.
Carboplatin has also been used to treat testicular cancer patients with stage 1 seminoma. Recent research indicates that this treatment is more effective and has fewer side effects than adjuvant radiotherapy.[6][7][8] It is as effective as radiotherapy at preventing development of seminoma in the remaining testicle.[9]
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| リンク元 | 「カルボプラチン」 |
| 関連記事 | 「CBD」 |
http://www.info.pmda.go.jp/go/pack/4291403F1026_2_14/ http://www.info.pmda.go.jp/go/pack/4291403A1088_1_03/