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 详细处方信息以本药内容附件PDF文件（2010102719370018.pdf）的“原文Priscribing Information”为准
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部分中文非诺多泮处方资料（仅供参考）

中文名称：甲磺酸非诺多泮

中文别名：6-氯-2,3,4,5-四氢-1-(4-羟苯基)-1H-3-苯并氮杂卓-7,8-二醇甲磺酸盐

英文名称：Fenoldopam mesylate

英文别名：8-Chloro-2-(4-hydroxyphenyl)-4-azabicyclo[5.4.0]undeca-7,9,11-triene-9,10-diol methanesulphonate

用途：非诺多泮可以增加去甲肾上腺素的血浆浓度。主要刺激DA1受体诱导小动脉扩张。既可降低动脉压，又可扩张肾血管致肾血流增加。

药理作用：非诺多泮是一快速作用的血管扩张剂，是 DA1 受体激动剂，与 α2- 肾上腺素受体有中度结合力，与 DA2 、 α1 和 β 肾上腺素受体、 5HT1 和 5HT2 受体或毒覃碱受体没有明显亲和力。非诺多泮是一种消旋混合物， R －异构体具有生物活性。 R- 异构体与 DA1 受体的亲和力较 S- 异构体高 250 倍。非诺多泮研究中，本品对突触前 DA2 受体、 α 或 β- 肾上腺素受体没有亲和力，对血管紧张素转化酶也无活性。非诺多泮可以增加去甲肾上腺素的血浆浓度。
　　本品主要刺激 DA1 受体诱导小动脉扩张。既可降低动脉压，又可扩张肾血管致肾血流增加。此外，本品作用于肾小细胞，具有直接的促尿钠排泄和利尿特性，特别是对高血压病人此作用更为明显。
　　本品静脉注射起效时间约为 5 分钟，约 20 分钟达到稳态血药浓度，经肝脏迅速代谢为无活性代谢产物，而后大部分由尿排泄，血浆清除半衰期约为 5 分钟。

适应症：严重高血压的紧急短期处理。

项目概述：一项随机双盲、安慰剂 对照研究中， 32 名轻中度原发性高血压患者（舒张期血压在 95-119mmHg 之间）分为 5 组，患者的平均基础血压 154/98mmHg ，心率为 75 下 / 分钟，以恒定的速率静脉滴注非诺多泮，收缩期和舒张期血压产生剂量相关性减少。以固定速率滴注 48 小时。所有滴速均快速产生反应，所有试验组中 15 分钟产生的效应是 1 小时时产生效应的 50 － 100 ％。在两个高剂量组中 48 小时时产生部分耐受，但是实质性影响持续至 48 小时。当滴注停止后血压渐渐恢复至治疗前水平，并未出现反跳现象。这一研究表明以 0.8μg/kg/min 的速率滴注并不比 0.4μg/kg/min 速率滴注反应强。
　　一项多中心、随机、双盲比较试验中， 94 名高血压急症患者（定义为舒张压 ≥120mmHg ，伴有末端器官损害，包括心血管、肾脏、大脑和视网膜系统）以 4 种速率（ 0.01 、 0.03 、 0.1 、 0.3μg/kg/min ）静脉滴注非诺多泮 24 小时。如果临床允许，在滴注后 1 小时滴速可加倍。结果显示收缩压和舒张压出现剂量依赖性快速降低，心率增加。
　　一项有 153 例严重高血压（舒张压 ≥16kPa ）病人参与的随机开放性多中心研究发现，本品与硝普钠疗效相仿。本品灌注引起的剂量相关性动脉压降低可达 24 小时，未见耐受性方面的不良反应，也未见停药反跳现象和明显的心率变化。对某些严重高血压伴肾功能损害的病人，本品可改善其肾功能。本品还可降低接受心脏或非心脏外科手术病人的术后高血压，能维持或增加排尿量。

市场分析：近些年，严重高血压的治疗在临床上越来越受到关注和重视，成为心血管科医生和新药开发机构研究的重要目标。目前，国内临床上常用的此类药物主要是硝普钠。但是，硝普钠在临床使用过程中存在很多问题，给患者和医生带来极大的不方便。如在使用硝普钠过程中可出现不同程度的恶心、呕吐、精神不安、肌肉痉挛、头痛、厌食、皮疹、出汗、发热等。长期或大量使用，特别是在肾功能衰竭病人中，可能引起硫氰化物蓄积而导致甲状腺功能减退，甚至出现险峻的低血压症。突然停药可出现反跳现象。再加上硝普钠性质不稳定，使用过程中见光易变质，这些缺点在很大程度上限制了它的使用。而非诺多泮由于性质稳定、疗效可靠，安全性高、不良反应甚微等优势在上市后的短短两年间就被收载进了美国药典（ USP ） 24 版（ 2000 年）增补版。总之，随着严重高血压的发病人群不断扩增，随着人们对严重高血压的认识不断加深，非诺多泮必将作为治疗该病的一线药物取代硝普钠的市场。
 
Fenoldopam Mesylate
Pronunciation: (feh-NAHL-doe-pam MEH-sih-LATE)
Class: Antihypertensive
Trade Names:
Corlopam
- Injection, concentrate 10 mg/mL

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Pharmacology
D 1 -like dopamine receptor agonist and binds with moderate affinity to α 2 -adrenoceptors.

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Pharmacokinetics
Absorption
Steady-state levels are attained in approximately 20 min (4 t ½ s) and are proportional to the infusion rate.

Metabolism
Conjugated by methylation, glucuronidation, and sulfation.

Elimination
Elimination t ½ is about 5 min in mild to moderate hypertension. Approximately 90% of infused dose is eliminated in urine and 10% in feces. About 4% is excreted unchanged. In pediatric patients, 1 mo to 12 yr of age, the elimination t ½ and Cl were 3 to 5 min and 3 L/h/kg, respectively.

Onset
Rapid onset and quickly reversible. Most of the effect of a given infusion rate is attained in 15 min.

Special Populations
Renal Function Impairment
Cl not altered in adult patients with end-stage renal disease.

Hepatic Function Impairment
Cl not altered in adult patients with severe hepatic failure.

Elderly
Pharmacokinetics not altered by age.

Gender
Pharmacokinetics not altered by gender.

Race
Pharmacokinetics not altered by race.

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Indications and Usage
Adults
Short-term (up to 48 h), in-hospital management of severe hypertension when rapid, but quickly reversible, emergency reduction of BP is indicated, including malignant hypertension with deteriorating end-organ function.

Children
Short-term (up to 4 h), in-hospital reduction in BP.

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Contraindications
Standard considerations.

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Dosage and Administration
Adults
IV In general, doses below 0.1 mcg/kg/min have modest effects and appear marginally useful in acutely hypertensive patients. As the initial dose increases, there is a greater and more rapid BP reduction. Lower initial doses (0.03 to 0.1 mcg/kg/min) slowly titrated have been associated with less reflex tachycardia than higher initial doses (0.3 mcg/kg/min or more). Most of the effect of a given infusion rate is attained in 15 min.

Children
IV In clinical trials, the usual starting dose was 0.2 mcg/kg/min with an effect on mean arterial pressure (MAP) evident within 5 min. At a constant infusion rate, the effect was maximal after 20 to 25 min. Increased dosages up to 0.3 to 0.5 mcg/kg/min q 20 to 30 min were generally well tolerated. Tachycardia without further decrease in MAP occurred at dosages greater than 0.8 mcg/kg/min. Upon discontinuation, and after an average of 4 h of therapy, BP and heart rate returned to near baseline within 30 min.

General Advice
Contents of ampule must be diluted before infusion; each ampule is for single use only.
Only dilute in sodium chloride 0.9% injection or dextrose 5% injection.
Dose must be individualized based on body weight and desired rapidity and extent of pharmacologic effect.
Do not administer if particulate matter or cloudiness noted.

Adults
Administer by continuous IV infusion, not by bolus.
Avoid hypotension and rapid decreases of BP.
Infusion can be abruptly discontinued or gradually tapered prior to discontinuation.
Use of a calibrated, mechanical continuous infusion pump is recommended for proper control of infusion rate.

Children
Administer IV by continuous infusion pump appropriate for the delivery of low infusion rates.

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Storage/Stability
Store ampules at 35.6° to 86°F. Diluted solution is stable under normal temperature and ambient light for at least 24 h. Discard unused, diluted solution within 24 h.

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Drug Interactions
Beta-blockers (eg, propranolol)
If possible, avoid coadministration with fenoldopam because of possible hypotension caused by beta-blocker inhibition of the sympathetic reflex response to fenoldopam.

Concomitant antihypertensive agents (eg, alpha-blockers, ACE inhibitors, calcium channel-blockers, diuretics)
Limited experience available.

Laboratory Test Interactions
None well documented.

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Adverse Reactions
Cardiovascular
Hypotension (at least 5%); angina pectoris, bradycardia, extrasystole, heart failure, ischemic heart disease, MI, palpitations (0.5% to 5%).

CNS
Headache (at least 5%); pyrexia (0.5% to 5%).

Dermatologic
Flushing (at least 5%).

GI
Nausea (at least 5%).

Genitourinary
Oliguria (0.5% to 5%).

Hematologic-Lymphatic
Bleeding, leukocytosis (0.5% to 5%).

Metabolic-Nutritional
Elevated BUN, LDH, serum glucose, and transaminase (0.5% to 5%).

Musculoskeletal
Limb cramp (0.5% to 5%).

Respiratory
Dyspnea, upper respiratory disorder (0.5% to 5%).

Miscellaneous
Nonspecific chest pain (0.5% to 5%).

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Precautions
Monitor
Monitor heart rate and BP of children continuously, usually by way of an intra-arterial line.
 
Pregnancy
Category B .

Lactation
Undetermined.

Children
Antihypertensive effects have not been studied in children 12 to 16 yr of age. Consider the patient's clinical condition and concomitant drug therapy during dose selection.

Elderly
Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Sulfite Sensitivity
Product contains metabisulfite and can cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes, in susceptible people.

CV
Dose-related tachycardia may occur, particularly with infusion rates greater than 0.l mcg/kg/min. Symptomatic hypotension may occur. Hypotension and tachycardia are the most common adverse reactions in children during short-term administration (30 min).

Hypokalemia
Decreases in serum potassium below 3 mEq/L may occur.

IOP
Because dose-dependent increases in IOP may occur with fenoldopam infusion (peak effect mean increase of 6.5 mm Hg), use with caution in patients with glaucoma or intraocular hypertension.

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Overdosage
Symptoms
Excessive hypotension.

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Patient Information
Caution patient that this item contains sulfite that can cause allergic reactions in certain individuals (eg, asthma patients).
Instruct patient to inform health care provider of glaucoma, increased IOP, or beta-blocker use before administration of this medicine.

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 详细处方信息以本药内容附件PDF文件（2010102719370018.pdf）的“原文Priscribing Information”为准
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2010-10-28更新