化工社化工社 化学情報印刷レポート · 研究参考用
フェロジピン
2,6-ジメチル-4-(2,3-ジクロロフェニル)-1,4-ジヒドロピリジン-3,5-ジカルボン酸3-エチル5-メチル · フェロジピン · 2,6-ジメチル-4-(2,3-ジクロロフェニル)-1,4-ジヒドロピリジン-3,5-ジカルボン酸3-メチル5-エチル · 4-(2,3-ジクロロフェニル)-2,6-ジメチル-1,4-ジヒドロピリジン-3,5-ジカルボン酸3-メチル5-エチル · 4-(2,3-ジクロロフェニル)-1,4-ジヒドロ-2,6-ジメチルピリジン-3,5-ジカルボン酸3-メチル5-エチル · スプレンジール · 4-(2,3-ジクロロフェニル)-1,4-ジヒドロ-2,6-ジメチル-5-メトキシカルボニル-3-ピリジンカルボン酸エチル · 1,4-ジヒドロ-2,6-ジメチル-4-(2,3-ジクロロフェニル)ピリジン-3,5-ジカルボン酸3-エチル5-メチル
識別子と物理属性
| CAS No. | 72509-76-3 |
|---|---|
| 分子式 | C18H19Cl2NO4 |
| 平均分子量 | 384.2 g/mol |
| 単同位体質量 | 383.0691135 g/mol |
| SMILES | CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cccc(Cl)c1Cl |
| InChIKey | RZTAMFZIAATZDJ-UHFFFAOYSA-N |
| PubChem CID | 3333 |
| ChEMBL | CHEMBL1480 |
| ChEBI | CHEBI:585948 |
| EC No. | 620-472-7 |
| DTXSID | DTXSID4023042 |
| 現地名 | フェロジピン |
化学・物理的性質
| XLogP | 3.9 |
|---|---|
| 極性表面積 | 64.6 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 5 |
| 回転可能結合数 | 6 |
| 重原子数 | 25 |
| 形式電荷 | 0 |
| 複雑度 | 614 |
| LogP（分配係数） | 3.86 |
| 溶解度 | 19.77.15e-03 g/LDMSO: 28 mg/mL不溶性 |
| 融点 | 145145 °C142-145°C |
| Caco2 Permeability | -4.64 |
| Physical Description | Solid |
| Kovats Retention Index | 2718.22678 |
| 沸点 | 471.5±45.0 °C(Predicted) |
| 密度 | 1.3506 (rough estimate) |
| 屈折率 | 1.6500 (estimate) |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | 個体 |
| pKa（酸解離定数） | 2.73±0.70(Predicted) |
| 色 | ライトイエロー |
| 安定性 | -20°C の DMSO またはエタノール溶液で最大 3 か月間保存できます。 |
| 主な用途 | 医薬品医薬品低分子化合物 |
| InChI | InChI=1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3 |
| InChIKey | RZTAMFZIAATZDJ-UHFFFAOYSA-N |
| SMILES | C1(C)NC(C)=C(C(OC)=O)C(C2=CC=CC(Cl)=C2Cl)C=1C(OCC)=O |
| CAS データベース | 72509-76-3(CAS DataBase Reference) |
| NISTの化学物質情報 | Felodipine(72509-76-3) |
化学的特性
White or Light Yellow Crystalline Powder
安全性と法規制
| GHS 分類 | WarningH302 (93.2%): Harmful if swallowed [Warning Acute toxicity, oral]H361 (22%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]H373 (22%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]H410 (15.3%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 59 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 4 (93.2%)Repr. 2 (22%)STOT RE 2 (22%)Aquatic Chronic 1 (15.3%) |
| 有害作用 | The adverse effects of felodipine are classified as either dose-dependent or dose-independent.* The common dose-dependent adverse effects of felodipine include peripheral edema, flushing, palpitations, and headaches. The most common clinical side effect of Felodipine use is peripheral edema. The frequency of peripheral edema is higher in individuals taking a higher dose of felodipine and elderly individuals. The incidence of peripheral edema is about 30% in elderly patients taking 20 mg of felodipine daily. Felodipine selectively dilates the arterioles, which increases intra-capillary pressure, causing extravasation of fluid into the interstitial space and resulting in peripheral edema. ACE inhibitors or angiotensin receptor blockers can prevent peripheral edema. Flushing and headaches also occur because of the vasodilatory effects of felodipine. Palpitations may occur because of reflex tachycardia.* In older adults with hypertension, initiating CCBs like felodipine frequently triggers a prescribing cascade, resulting in the subsequent unnecessary prescription of diuretics. Evaluating whether the edema is attributed to an underlying medical condition or is a result of Felodipine use is a risk mitigation strategy.* The dose-independent adverse effects of felodipine include fatigue, nausea, and gingival hyperplasia. Gingival hyperplasia occurs in less than 1% of patients and is more common in individuals with poor dental hygiene. The mechanism of gingival hyperplasia is overexpression of growth factors due to high concentrations of calcium ions, leading to fibroblast proliferation and chronic inflammatory cell infiltration. Gingival hyperplasia is usually reversible on discontinuation of felodipine.Drug-Drug InteractionsCytochrome P450 3A4 metabolizes felodipine.* The plasma level of felodipine increases when used in conjunction with CYP 3A4 inhibitors such as azole antifungals (Itraconazole and Ketoconazole), macrolide antibiotics (Clarithromycin and Azithromycin), HIV protease inhibitors, immunosuppressants (Cyclosporine), Cimetidine, or grapefruit juice.* The plasma level and efficacy of felodipine decrease when co-administered with CYP3A4 inducers such as anticonvulsants (Phenytoin and Carbamazepine), St John’s wort, or rifampicin.* When Metoprolol is subsequently administered with a conventional Felodipine formulation to treat essential hypertension, the plasma concentration of Metoprolol increases while that of felodipine remains unchanged.* If felodipine is co-administered with Theophylline, it results in a decrease in the plasma concentration of Theophylline.* CCBs and statins are frequently prescribed in patients with cardiovascular risk factors. In a study, acute kidney injury, hyperkalemia, acute myocardial infarction, and acute ischemic stroke were increased due to interaction between CYP3A4-metabolized statins and CCBs that inhibit CYP3A4, like Felodipine. |
| 毒性の概要 | A mild-to-moderate overdose of felodipine can result in hypotension secondary to peripheral vasodilation and reflex tachycardia. However, a severe overdose of felodipine can cause life-threatening profound hypotension and bradycardia. Case fatality due to profound, refractory circulatory collapse overdose has been reported in the literature. The risk of overdose increases in elderly individuals, patients with liver impairment, and concomitant administration of felodipine with beta blockers. Overdose symptoms can include lightheadedness, syncope, altered mental status, and shock secondary to profound hypotension. The insulin release from the pancreas depends on calcium influx through the L-type channels. Felodipine blocks these calcium channels and results in hyperglycemia because of decreased insulin release.The first step in managing Felodipine overdose is maintaining a patent airway. Patients who have consumed an excess of felodipine ER tablets but have not yet developed any symptoms should be started on gastrointestinal decontamination with whole bowel irrigation if they present within 6 to 8 hours of drug ingestion. Patients with hypotension should undergo resuscitation with IV fluids. However, caution is necessary for individuals with congestive heart failure and pulmonary edema. Vasopressor therapy with dopamine or norepinephrine is an as-needed option for hypotension. IV calcium gluconate or calcium chloride (given via central line) are also options in treating Felodipine overdose.In patients with severe overdose, atropine should be administered IV for bradycardia. The vital signs, serum electrolytes, especially potassium, blood glucose, urine output, and ECG, should be monitored regularly. Hyperinsulinemia-euglycemia therapy is also an established treatment for CCB overdose. This therapy helps mobilize glucose from the peripheral tissue to serve as an alternative energy source for the myocardium. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)FelodipinevLess-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during LactationBecause no information is available on the use of felodipine during breastfeeding, an alternate drug may be preferred.◉ Effects in Breastfed InfantsRelevant published information was not found as of the revision date.◉ Effects on Lactation and Breastmilk |
| 水環境危害等級（WGK） | 3 |
| RTECS 番号 | US7968700 |
| 輸送番号（UN） | UN 3077 9 / PGIII |
| 税関コード | 29333990 |
| 危険文句（R） | 22 |
| 危険表示 | Xn |
| 安全措置（S） | 36 |
| 危険等級 | Acute Tox. 4 OralAquatic Acute 1Aquatic Chronic 1Repr. 2STOT RE 2 Inhalation |
| 貯蔵分類 | 11 - Combustible Solids |
用途
用途
フェロジピン（Felodipine）は、高血圧の制御のために用いられるカルシウム拮抗剤である。
説明
Felodipine is a vasodilatory calcium antagonist with a high degree of vascular selectivity. It is currently indicated for use only in hypertension, either as monotherapy or in conjunction with diuretics or beta blockers.
使用
Felodipine is used as a dihydropyridine calcium channel blocker. It displays high vascular selectivity; lowers arterial blood pressure without altering cardiac contractility. Antihypertensive.
一般的な説明
Felodipine, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethylmethyl ester (Plendil), is a second-generation dihydropyridinechannel blocker of the nifedipine type. It is more selectivefor vascular smooth muscle than for myocardial tissueand serves as an effective vasodilator.