Natrecor（奈西利肽nesiritide）注射剂一类新的血管扩张剂
奈西利肽(（nesiritide/Natrecor）一类新的血管扩张剂，在急性心力衰竭的治疗中一种重组人脑钠肽或B型利钠肽（BNP），与内生荷尔蒙完全相同。奈西利肽有静脉、动脉和冠状血管舒张作用以减轻前后负荷并在无直接正性肌力作用的情况下增加心输出量。

在慢性心力衰竭的患者中静注奈西利肽可通过促进钠外排和抑制肾素-血管紧张素-醛固酮系统和交感神经系统而产生有益的血液动力学作用。奈西利肽与静脉注射硝酸甘油比较可更有效地改善血液动力学并具有较少不良反应，虽然其并没有转变为改善临床结果。

奈西利肽（nesiritide/Natrecor）可能导致低血压并且一些病人可能对其无反应。
奈西利肽（nesiritide/Natrecor）系美国Scios公司研发的重组人B型利钠肽（γBNP），主要用于急性失代偿性充血性心力衰竭时呼吸困难的治疗。

奈西利肽（nesiritide/Natrecor）系美国Scios公司研发的重组人B型利钠肽（γBNP），主要用于急性失代偿性充血性心力衰竭时呼吸困难的治疗。

■药理作用

B型利钠肽（BNP）是心室分泌的心脏天然激素，不仅可以促进水、电解质经肾的排泄，而且还有诱导血管扩张的作用。γBNP与血管平滑肌和内皮细胞的不溶性鸟苷酸环化酶受体结合，导致细胞内3’，5’－环鸟苷－磷酸（cGMP）浓度的增加，引起平滑肌细胞的松弛。研究显示，γBNP可降低心脏前、后负荷，改善慢
性心脏病人急性发作时的症状，具有强心和扩张血管作用。对于改善充血性心力衰竭（CHF）病人的血液动力学，如动脉和静脉扩张、增加钠排泄以及抑制肾素－血管紧张素－醛固酮和交感神经系统有较好的作用。

■药动学
药动学研究显示，CHF病人给予本品静滴或静注，平均终末消除半衰期约为8分钟，平均初始消除相约为两分钟。本品病人给药后的中央室平均分布容积约为0.073升/千克，稳态分布容积为0.19升/千克，平均清除率约为9.2毫升/分·千克。本品注射每分钟每公斤体重为0.01～0.03微克达到稳态时，血浆BNP可比基线增加约3～6倍。

■临床评价
多项临床研究评价了本品用于CHF病人的疗效。其中一项临床研究的对象为432例失代偿性CHF住院病人，另一项为有305例病人参与的对照研究，病人均随机分组。结果提示，低剂量本品组肺毛细血管楔压较安慰剂组有较为明显的下降；低剂量和高剂量本品组临床情况改善较安慰剂组显著；用药组病人于6小时时呼吸困难和疲乏减轻。一项有127例病人参与的Ⅲ期临床安慰剂对照研究结果表明，本品使急性心肌梗死病人的血流动力学指数和心衰症状明显改善。病人随机接受本品每分钟0.015微克/千克或0.03微克/千克静注，肺动脉楔压分别降低20％或31％。

■不良反应

本品最常见的不良反应为剂量相关性低血压，通常无症状或症状轻微。输注后24小时内可能发生的不良反应有：低血压、室性心动过速（异常快速心率）、心绞痛（胸痛）、心搏徐缓（异常慢速心率）、头痛、腹痛、背痛、失眠、头晕、焦虑、恶心、呕吐等。

NATRECOR® helps patients with heart failure when their condition worsens to the point that they have difficulty breathing when they are not active (like when they are resting in bed) or when they engage in slight physical activity (like brushing their teeth). Administered directly into the bloodstream (intravenously) of patients who experience such an episode, NATRECOR® relaxes the muscles that surround blood vessels, resulting in improved blood flow throughout the body without causing one's heartbeat to increase or become irregular. 

FOR INTRAVENOUS INFUSION ONLY

DESCRIPTION

Natrecor®(nesiritide) is a sterile, purified preparation of a new drug class, human B-type natriuretic peptide (hBNP), and is manufactured fromE.coliusingrecombinant DNA technology. Nesiritide has a molecular weight of 3464 g/mol and an empirical formula of C143H244N50O42S4.Nesiritide has the same 32 amino acid sequence as the endogenous peptide, which is produced by the ventricular myocardium.

Natrecor is formulated as the citrate salt of rhBNP, and is provided in a sterile, single-use vial. Each 1.5 mg vial contains awhite- to off-white lyophilized powder for intravenous (IV) administration after reconstitution.

Thequantitativecomposition of the lyophilized drug per vial is: nesiritide 1.58 mg, mannitol 20.0 mg, citric acid monohydrate 2.1 mg, and sodium Important Safety Information

HYPOTENSION

NATRECOR® (nesiritide) may cause hypotension and should be administered only in settings where blood pressure can be monitored closely. If hypotension occurs during administration of NATRECOR®,the dose should be reduced or discontinued. At the recommended dose of NATRECOR®, the incidence of symptomatic hypotension (4%) was similar to that of IV nitroglycerin (5%). Asymptomatic hypotension occurred in 8% of patients treated with either drug. In some cases, hypotension that occurs with NATRECOR® may be prolonged. The mean duration of symptomatic hypotension was longer with NATRECOR® than IV nitroglycerin (2.2 versus 0.7 hours, respectively). NATRECOR® should not be used in patients with systolic blood pressure <90 mm Hg or as primary therapy in patients with cardiogenic shock. The rate of symptomatic hypotension may be increased in patients with a baseline blood pressure <100 mm Hg, and NATRECOR® should be used cautiously in these patients. In earlier trials, when NATRECOR® was initiated at doses higher than the 2 mcg/kg bolus followed by a 0.01 mcg/kg/min infusion, the frequency, intensity, and duration of hypotension were increased. The hypotensive episodes were also more often symptomatic and/or more likely to require medical intervention.

NATRECOR® is not recommended for patients for whom vasodilating agents are not appropriate and should be avoided in patients with low cardiac filling pressures.

RENAL

NATRECOR® may affect renal function in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with NATRECOR® may be associated with azotemia. In the VMAC trial, through day 30, the incidence of elevations in creatinine to >0.5 mg/dL above baseline was 28% and 21% in the NATRECOR® and nitroglycerin groups, respectively. When NATRECOR® was initiated at doses higher than 0.01 mcg/kg/min, there was an increased rate of elevated serum creatinine over baseline compared with standard therapies, although the rate of acute renal failure and need for dialysis were not increased.

MORTALITY

In seven NATRECOR® clinical trials, through 30 days, 5.5% in the NATRECOR® treatment group died as compared with 4.3% in the group treated with other standard medications. In five clinical trials, through 180 days, 21.5% in the NATRECOR® treatment group died as compared with 20.7% in the group treated with other medications. There is not enough information to know if there is an increased risk of death after treatment with NATRECOR®.