规格 | 价格 | |
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100mg | ||
500mg |
药代性质 (ADME/PK) |
Absorption, Distribution and Excretion
Rapidly absorbed with peak plasma concentrations occurring approximately 1 hour after oral administration. Bioavailability is 65-75%. Following absorption, perindopril is hydrolyzed to perindoprilat, which has an average bioavailability of 20%. The rate and extent of absorption is unaffected by food. However, food decreases the extent of biotransformation to peridoprilat and reduces its bioavailability by 35%. Perindopril is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine. 219 - 362 mL/min [oral administration] Metabolism / Metabolites Extensively metabolized, with only 4-12% of the dose recovered in urine following oral administration. Six metabolites have been identified: perindoprilat, perindopril glucuronide, perindoprilat glucuronide, a perindopril lactam, and two perindoprilat lactams. Only perindoprilat is pharmacologically active. Peridoprilat and perindoprilat glucuronide are the two main circulating metabolites. Perindopril has known human metabolites that include Perindoprilat glucuronide. Biological Half-Life Perindopril, 1.2 hours; Peridoprilat, 30-120 hours. The long half life of peridoprilat is due to its slow dissociation from ACE binding sites. |
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毒性/毒理 (Toxicokinetics/TK) |
Hepatotoxicity
Perindopril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations ( Likelihood score: E* (unproved but suspected rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Limited information indicates that only low levels of perindopril and its active metabolite are found in breastmilk, which is consistent with other drugs in this class. Amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. ◉ Effects in Breastfed Infants Ten infants were breastfed (extent not stated) by mothers were taking perindopril 5 to 20 mg daily. All infants grew and developed normally according to their parents. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Perindoprilat, 10-20% bound to plasma proteins |
参考文献 |
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其他信息 |
Perindopril is an alpha-amino acid ester that is the ethyl ester of N-{(2S)-1-[(2S,3aS,7aS)-2-carboxyoctahydro-1H-indol-1-yl]-1-oxopropan-2-yl}-L-norvaline It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor and an antihypertensive agent. It is an alpha-amino acid ester, a dicarboxylic acid monoester, an organic heterobicyclic compound and an ethyl ester. It is a conjugate acid of a perindopril(1-).
Perindopril is a nonsulfhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to perindoprilat, its active metabolite, following oral administration. Perindoprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Perindopril may be used to treat mild to moderate essential hypertension, mild to moderate congestive heart failure, and to reduce the cardiovascular risk of individuals with hypertension or post-myocardial infarction and stable coronary disease. Perindopril is an Angiotensin Converting Enzyme Inhibitor. The mechanism of action of perindopril is as an Angiotensin-converting Enzyme Inhibitor. Perindopril is an angiotensin-converting enzyme (ACE) inhibitor used in the therapy of hypertension and stable coronary artery disease. Perindopril is associated with a low rate of transient serum aminotransferase elevations and has been linked to rare instances of acute liver injury. Perindopril is a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Upon hydrolysis, perindopril is converted to its active form perindoprilat, inhibiting ACE and the conversion of angiotensin I to angiotensin II; consequently, angiotensin II-mediated vasoconstriction and angiotensin II-stimulated aldosterone secretion from the adrenal cortex are inhibited and diuresis and natriuresis ensue. An angiotensin-converting enzyme inhibitor. It is used in patients with hypertension and heart failure. See also: Perindopril Erbumine (has salt form). Drug Indication For the treatment of mild to moderate essential hypertension, mild to moderate congestive heart failure, and to reduce the cardiovascular risk of individuals with hypertension or post-myocardial infarction and stable coronary disease. FDA Label Mechanism of Action There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Perindoprilat, the active metabolite of perindopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Perindopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. |
分子式 |
C₁₉H₃₂N₂O₅
|
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分子量 |
368.47
|
精确质量 |
368.231
|
CAS号 |
82834-16-0
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相关CAS号 |
Perindopril erbumine;107133-36-8
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PubChem CID |
107807
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外观&性状 |
Off-white to light yellow solid powder
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密度 |
1.1±0.1 g/cm3
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沸点 |
537.4±45.0 °C at 760 mmHg
|
熔点 |
100-101°C
|
闪点 |
278.8±28.7 °C
|
蒸汽压 |
0.0±3.1 mmHg at 25°C
|
折射率 |
1.512
|
LogP |
3.36
|
tPSA |
95.94
|
氢键供体(HBD)数目 |
2
|
氢键受体(HBA)数目 |
6
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可旋转键数目(RBC) |
9
|
重原子数目 |
26
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分子复杂度/Complexity |
524
|
定义原子立体中心数目 |
5
|
SMILES |
CCC[C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O
|
InChi Key |
IPVQLZZIHOAWMC-QXKUPLGCSA-N
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InChi Code |
InChI=1S/C19H32N2O5/c1-4-8-14(19(25)26-5-2)20-12(3)17(22)21-15-10-7-6-9-13(15)11-16(21)18(23)24/h12-16,20H,4-11H2,1-3H3,(H,23,24)/t12-,13-,14-,15-,16-/m0/s1
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化学名 |
(2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid
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别名 |
S 9490; S-9490
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外实验) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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溶解度 (体内实验) |
注意: 如下所列的是一些常用的体内动物实验溶解配方,主要用于溶解难溶或不溶于水的产品(水溶度<1 mg/mL)。 建议您先取少量样品进行尝试,如该配方可行,再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80: Saline = 10 : 5 : 85 (如: 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备:将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中,得到澄清溶液。 注射用配方 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (如: 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如: 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液,加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如:100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中,得到0.5%CMC-Na澄清溶液;然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中,得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) 请根据您的实验动物和给药方式选择适当的溶解配方/方案: 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 2.7139 mL | 13.5696 mL | 27.1393 mL | |
5 mM | 0.5428 mL | 2.7139 mL | 5.4279 mL | |
10 mM | 0.2714 mL | 1.3570 mL | 2.7139 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
计算结果:
工作液浓度: mg/mL;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。