(3S)-4-[(2S)-1-[[(1R,2aS,4S,5aS,8aS,11aS,13S,14aS,16S,17aR,19S,20aS,25S,26aS,29aS,31S,32aS,34S,35aS,37R,38aS,41aS,42R,44aS,45S,47aS,48S,50aS,51S,53aS,54R,56aS,57S,59aS,60S,62aS,63S,66S,69S,72S,75S,78S,81S,84S,87S,90S,93R)-29a,62a,69,84-tetrakis(4-aminobutyl)-8a,41a,72-tribenzyl-50a,53a-bis[(2S)-butan-2-yl]-47a,48,56a,81,90-pentakis(3-carbamimidamidopropyl)-31,60-bis(2-carboxyethyl)-42-[N-[2-[2-[(1S)-1-carboxyethyl]imino-2-hydroxyethyl]imino-2-hydroxyethyl]-C-hydroxycarbonimidoyl]-57-(carboxymethyl)-1a,3,4a,7a,10a,12,13a,15,16a,18,19a,22a,25a,28a,31a,33,34a,36,37a,40a,43a,44,46a,47,49a,50,52a,53,55a,56,58a,59,61a,62,64a,65,68,71,74,77,80,83,86,89,92,95,98-heptatetracontahydroxy-11a,13,45-tris[(1R)-1-hydroxyethyl]-35a,75,78-tris(2-hydroxy-2-iminoethyl)-14a-(3-hydroxy-3-iminopropyl)-66-(hydroxymethyl)-2a,16,38a,44a-tetrakis[(4-hydroxyphenyl)methyl]-26a,32a,59a,63,87-pentamethyl-20a,34-bis(2-methylpropyl)-51-(2-methylsulfanylethyl)-9,24,30-trioxo-5a-propan-2-yl-39,40,66a,67a,70a,71a-hexathia-a,2,3a,6a,8,9a,11,12a,14,15a,17,18a,21a,23,24a,27a,29,30a,32,33a,35,36a,39a,42a,43,45a,46,48a,49,51a,52,54a,55,57a,58,60a,61,63a,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazahexacyclo[91.71.4.454,117.04,8.019,23.025,29]doheptacontahecta-a(1a),2,3a(4a),6a(7a),9a(10a),11,12a(13a),14,15a(16a),17,18a(19a),21a(22a),24a(25a),27a(28a),30a(31a),32,33a(34a),35,36a(37a),39a(40a),42a(43a),43,45a(46a),46,48a(49a),49,51a(52a),52,54a(55a),55,57a(58a),58,60a(61a),61,63a(64a),64,67,70,73,76,79,82,85,88,91,94,97-heptatetracontaen-37-yl]imino]-1-hydroxy-3-phenylpropan-2-yl]imino-3-[[[(2S)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]-hydroxymethylidene]amino]-4-hydroxybutanoic acid

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: (3S)-4-[(2S)-1-[[(1R,2aS,4S,5aS,8aS,11aS,13S,14aS,16S,17aR,19S,20aS,25S,26aS,29aS,31S,32aS,34S,35aS,37R,38aS,41aS,42R,44aS,45S,47aS,48S,50aS,51S,53aS,54R,56aS,57S,59aS,60S,62aS,63S,66S,69S,72S,75S,78S,81S,84S,87S,90S,93R)-29a,62a,69,84-tetrakis(4-aminobutyl)-8a,41a,72-tribenzyl-50a,53a-bis[(2S)-butan-2-yl]-47a,48,56a,81,90-pentakis(3-carbamimidamidopropyl)-31,60-bis(2-carboxyethyl)-42-[N-[2-[2-[(1S)-1-carboxyethyl]imino-2-hydroxyethyl]imino-2-hydroxyethyl]-C-hydroxycarbonimidoyl]-57-(carboxymethyl)-1a,3,4a,7a,10a,12,13a,15,16a,18,19a,22a,25a,28a,31a,33,34a,36,37a,40a,43a,44,46a,47,49a,50,52a,53,55a,56,58a,59,61a,62,64a,65,68,71,74,77,80,83,86,89,92,95,98-heptatetracontahydroxy-11a,13,45-tris[(1R)-1-hydroxyethyl]-35a,75,78-tris(2-hydroxy-2-iminoethyl)-14a-(3-hydroxy-3-iminopropyl)-66-(hydroxymethyl)-2a,16,38a,44a-tetrakis[(4-hydroxyphenyl)methyl]-26a,32a,59a,63,87-pentamethyl-20a,34-bis(2-methylpropyl)-51-(2-methylsulfanylethyl)-9,24,30-trioxo-5a-propan-2-yl-39,40,66a,67a,70a,71a-hexathia-a,2,3a,6a,8,9a,11,12a,14,15a,17,18a,21a,23,24a,27a,29,30a,32,33a,35,36a,39a,42a,43,45a,46,48a,49,51a,52,54a,55,57a,58,60a,61,63a,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazahexacyclo[91.71.4.454,117.04,8.019,23.025,29]doheptacontahecta-a(1a),2,3a(4a),6a(7a),9a(10a),11,12a(13a),14,15a(16a),17,18a(19a),21a(22a),24a(25a),27a(28a),30a(31a),32,33a(34a),35,36a(37a),39a(40a),42a(43a),43,45a(46a),46,48a(49a),49,51a(52a),52,54a(55a),55,57a(58a),58,60a(61a),61,63a(64a),64,67,70,73,76,79,82,85,88,91,94,97-heptatetracontaen-37-yl]imino]-1-hydroxy-3-phenylpropan-2-yl]imino-3-[[[(2S)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]-hydroxymethylidene]amino]-4-hydroxybutanoic acid
• 化学式: C₂₈₄H₄₃₂N₈₄O₇₉S₇
• 分子量: 6511.0
• InChiKey: ZPNFWUPYTFPOJU-LPYSRVMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -25.4
• 重原子数：
  454
• 可旋转键数：
  111
• 环数：
  15.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  2820
• 氢给体数：
  93
• 氢受体数：
  97

ADMET

代谢

抑肽酶会缓慢被溶酶体酶降解。抑肽酶的生理肾脏处理方式与其他小蛋白类似，例如胰岛素。

Aprotinin is slowly degraded by lysosomal enzymes. The physiological renal handling of aprotinin is similar to that of other small proteins, e.g., insulin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在研究中，对九名未经治疗的高血压患者进行了研究，静脉注射200万KIU的抑肽酶，在两小时内阻断了100毫克卡托普利的急性降压效果。

In study of nine patients with untreated hypertension, /aprotinin/ infused intravenously in a dose of 2 million KIU over two hours blocked the acute hypotensive effect of 100mg of captopril.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

抗纤溶剂和溶栓剂的作用是相互拮抗的；尽管抑肽酶可能对预防接受溶栓剂治疗的心脏手术患者出现严重出血有效...

The actions of antifibrinolytic agents and of thrombolytic agents are mutually antagonistic; although aprotinin may be effective in preventing severe hemorrhage in patients who have received a thrombolytic agent prior to cardiac surgery...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

氨基糖苷类抗生素或改变肾功能药物的联合使用增加了肾功能障碍和肾衰竭的风险。

Concomitant use of aminoglycoside antibiotics or drugs that alter renal function increased risk of renal dysfunction and renal failure.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

阿普特林干扰了肝素与血小板的结合，并减少了心肺旁路（CPB）期间的血液丢失。肝素在CPB期间消除了血小板的力量，而血小板力量在鱼精蛋白给药后的恢复程度似乎与血液丢失有关。本研究评估了阿普特林对肝素抑制血小板力量的影响。使用Hemodyne止血分析仪测量血小板力量。通过向富血小板血浆（PRP）中添加巴曲酶和10 mM CaCl(2)形成血栓。凝血条件包括pH 7.4，离子强度0.15 M，纤维蛋白原水平1 mg/ml和每微升75,000血小板。在凝血1200秒后，力量由7110+/-1190降至450+/-450 dyn，由0.2 U/mL肝素引起。含有阿普特林[20微g/mL（140 KIU/mL）]的PRP中的血小板力量未被肝素添加所抑制（7480+/-2410 dyn）。将阿普特林[40微g/mL（280 KIU/mL）]添加到先前肝素化的血浆中，抵消了肝素力量的抑制。阿普特林（40微g/mL）在没有肝素的PRP中增加了血小板力量，从5630增加到11,138+/-562。阿普特林不影响凝血酶活性、纤维蛋白结构、血小板聚集或分泌。阿普特林抵消了肝素对血小板力量的抑制，并在没有肝素的情况下增强了血小板力量。阿普特林-肝素-血小板相互作用可能有助于解释阿普特林在CPB期间减少血液丢失的能力。

Aprotinin interferes with heparin binding to platelets and decreases blood loss during cardiopulmonary bypass (CPB). Heparin abolishes platelet force during CPB, and the extent of platelet force recovery after protamine administration appears to correlate with blood loss. This study assessed the effect of aprotinin on heparin suppression of platelet force. Platelet force was measured using the Hemodyne Hemostasis Analyzer. Clots were formed from platelet-rich plasma (PRP) by the addition of batroxobin and 10 mM CaCl(2). Clotting conditions included pH 7.4, ionic strength 0.15 M, fibrinogen level 1 mg/ml and 75,000 platelets/microl. After 1200 s of clotting, force was reduced from 7110+/-1190 to 450+/-450 dyn by 0.2 U/mL of heparin. Platelet force in aprotinin [20 microg/mL (140 KIU/mL)] containing PRP was not suppressed by heparin addition (7480+/-2410 dyn). Aprotinin [40 microg/mL (280 KIU/mL)] addition to previously heparinized plasma counteracted heparin force suppression. Aprotinin (40 microg/mL) increased platelet force from 5630 to 11,138+/-562 in PRP devoid of heparin. Aprotinin did not affect thrombin activity, fibrin structure, platelet aggregation or secretion. Aprotinin counteracts heparin suppression of platelet force and enhances platelet force in the absence of heparin. Aprotinin-heparin-platelet interactions may help explain aprotinin's ability to reduce blood loss during CPB.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

过敏性休克或其他严重过敏反应需要立即紧急治疗，包括以下措施：静脉注射肾上腺素；吸氧；静脉注射抗组胺药；静脉注射皮质类固醇；气道管理（包括插管）。

Anaphylaxis or other severe allergic reactions require immediate emergency treatment, which consists of the following : Parenteral epinephrine; Oxygen; Parenteral antihistamines; Intravenous corticosteroids; Airway management (including intubation).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

静脉（iv）注射后，抗胰蛋白酶迅速分布到整个细胞外空间，导致血浆中抗胰蛋白酶浓度迅速初始下降。

After intravenous (iv) injection, rapid distribution of aprotinin occurs into the total extracellular space, leading to a rapid initial decrease in plasma aprotinin concentration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给予单次静脉注射放射性示踪的抑肽酶后，大约25-40%的放射性活性在48小时内通过尿液排出。在30分钟内输注100万KIU后，大约2%以未改变的药物形式排出。在更大剂量，即200万KIU在30分钟内输注后，未改变的抑肽酶通过尿液排出的比例大约占剂量的9%。

Following a single iv dose of radiolabelled aprotinin, approximately 25-40% of the radioactivity is excreted in the urine over 48 hours. After a 30 minute infusion of 1 million KIU, about 2% is excreted as unchanged drug. After a larger dose of 2 million KIU infused over 30 minutes, urinary excretion of unchanged aprotinin accounts for approximately 9% of the dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

动物研究表明，抑肽酶主要在肾脏中积累。抑肽酶在被肾小球过滤后，被近端小管积极重吸收，并储存在吞噬体中。

Animal studies have shown that aprotinin is accumulated primarily in the kidney. Aprotinin, after being filtered by the glomeruli, is actively reabsorbed by the proximal tubules in which it is stored in phagolysosomes.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

没有关于抑肽酶分布到母乳中的研究。

There are no available studies on the distribution of aprotinin into breast milk.

来源:Hazardous Substances Data Bank (HSDB)