Benazeprilat
(Synonyms: 苯那普利拉,CGS 14831) 目录号 : GC42913
An ACE inhibitor
Cas No.:86541-78-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Benazeprilat is an inhibitor of angiotensin-converting enzyme (ACE; IC50 = 0.28 nM in plasma from dog) and the active metabolite of the prodrug benazepril. [1] Benazeprilat is produced in the liver following cleavage of the ester group from benazepril. Formulations containing the prodrug benazepril have been used to treat hypertension in human and veterinary medicine.
Reference:
[1]. Toutain, P.L., and Lefèbvre, H.P. Pharmacokinetics and pharmacokinetic/pharmacodynamic relationships for angiotensin-converting enzyme inhibitors. J. Vet. Pharmacol. Ther. 27(6), 515-525 (2004).
| Cas No. | 86541-78-8 | SDF | |
| 别名 | 苯那普利拉,CGS 14831 | ||
| 化学名 | (3S)-3-[[(1S)-1-carboxy-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid | ||
| Canonical SMILES | O=C1[C@@H](N([H])[C@H](C(O)=O)CCC2=CC=CC=C2)CCC3=C(N1CC(O)=O)C=CC=C3 | ||
| 分子式 | C22H24N2O5 | 分子量 | 396.4 |
| 溶解度 | 0.5mg/mL in DMSO, 0.16mg/mL in DMF | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5227 mL | 12.6135 mL | 25.227 mL |
| 5 mM | 0.5045 mL | 2.5227 mL | 5.0454 mL |
| 10 mM | 0.2523 mL | 1.2614 mL | 2.5227 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Benazeprilat disposition and effect in dogs revisited with a pharmacokinetic/pharmacodynamic modeling approach
J Pharmacol Exp Ther 2000 Mar;292(3):1087-93.PMID:10688627doi
The pharmacokinetic disposition of Benazeprilat, an angiotensin-converting enzyme (ACE) inhibitor (ACEI), was assessed with a nonlinear binding model in dogs. A single oral benazepril dose, a single i.v. Benazeprilat dose, or a daily oral dose of benazepril for 14 consecutive days was administered. The activity of Benazeprilat was assessed by measuring plasma ACE inhibition with an ex vivo assay. Benazeprilat data were fitted to equations corresponding to a monocompartmental model with a volume equal to the extracellular space ( approximately 0.2 l/kg) in which a fraction of Benazeprilat was nonlinearily bound to ACE with both a saturable tissue and nontissue binding. The half-life of Benazeprilat elimination determined from this physiologically based model was 39 +/- 6 min. The estimated maximal binding capacity of Benazeprilat to ACE was approximately 23.5 nmol/kg, 90% of which was tissular. The estimated equilibrium constant of dissociation (K(d)) of Benazeprilat to ACE was 2.7 to 4.5 nM. IC(50) values were one order of magnitude lower than K(d) values (i.e., approximately 0.27 nM). The nonlinear disposition of Benazeprilat raised several issues and it was concluded that the Benazeprilat concentration profile was only relevant to definition of an optimal dosage regimen if the appropriate kinetic model was used to interpret the plasma data.
Pharmacokinetic/pharmacodynamic modeling of benazepril and Benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses
Res Vet Sci 2017 Oct;114:117-122.PMID:28371693DOI:10.1016/j.rvsc.2017.03.016.
Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) Benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and Benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of Benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of Benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, Benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated.
Hemodynamic effects of amlodipine and Benazeprilat in spontaneously hypertensive rats
J Cardiovasc Pharmacol 1993 Mar;21(3):405-11.PMID:7681501DOI:10.1097/00005344-199303000-00009.
We wished to assess the hemodynamic effects of administration of the combination of the calcium channel blocking agent amlodipine and the angiotensin-converting enzyme (ACE) inhibitor Benazeprilat in conscious spontaneously hypertensive rats (SHR). In SHR previously instrumented for measurement of mean arterial blood pressure (MAP) and heart rate (HR), intravenous (i.v.) injection of amlodipine (0.25-4 mg/kg) produced dose-dependent decreases in blood pressure (BP). Administration of Benazeprilat (0.1-10 mg/kg i.v.) decreased arterial MAP, and Benazeprilat (10 mg/kg) effectively blocked the effects of exogenously administered angiotensin I (AI). In animals surgically prepared for measurement of BP, HR, and hindquarter, renal, and mesenteric blood flows, administration (i.v.) of the combination of amlodipine (0.5 mg/kg) with Benazeprilat (10 mg/kg) evoked a decrease in BP that was greater than that elicited by monotherapy. The tachycardic response observed after administration of the combination was no different from that observed after monotherapy with amlodipine. Simultaneous administration of amlodipine and Benazeprilat produced reductions in vascular resistance in the hindquarter, renal and mesenteric beds that were greater than the responses evoked by injection of either agent. The major finding of these studies was that dual therapy with amlodipine and Benazeprilat produced an additive hypotensive effect in conscious SHR. Regional vasodilation accompanied the large degree of hypotension evoked by the combination.
Hemodynamic effects of Benazeprilat in the anesthetized dog with acute left ventricular failure
Jpn J Pharmacol 1991 Jul;56(3):369-75.PMID:1895581DOI:10.1254/jjp.56.369.
To examine the hemodynamic effects of benazepril, an angiotensin converting enzyme inhibitor, in left ventricular failure, its active metabolite Benazeprilat was administered during acute ischemic left ventricular failure in anesthetized open chest dog induced by repeated injections of plastic microspheres into the left coronary artery. The coronary embolization with microspheres resulted in a moderate and stable left ventricular pump failure characterized by increased left ventricular end-diastolic pressure (LVEDP) and decreased cardiac output (CO). Benazeprilat (30 micrograms/kg) administered intravenously after a stabilization period lowered LVEDP and maintained CO. The total peripheral resistance was reduced with Benazeprilat. The oxygen consumption and the coronary blood flow were reduced with Benazeprilat because of a decrease in wall tension and afterload. These results suggest that Benazeprilat (benazepril) has beneficial effects for the treatment of acute left ventricular failure.
Pharmacokinetic/pharmacodynamic modelling of the disposition and effect of benazepril and Benazeprilat in cats
J Vet Pharmacol Ther 2003 Jun;26(3):213-24.PMID:12755906DOI:10.1046/j.1365-2885.2003.00468.x.
The disposition and effect of benazepril and its active metabolite, Benazeprilat, were evaluated in cats using a pharmacokinetic/pharmacodynamic model. Cats received single 1 mg/kg doses of intravenous 14C-benazeprilat and oral 14C-benazepril.HCl, and single and repeat (eight daily) oral administrations of 0.25, 0.5 and 1.0 mg/kg nonlabelled benazepril.HCl. The pharmacokinetic endpoints were plasma concentrations of benazepril and Benazeprilat, and recovery of radioactivity in faeces and urine. The pharmacodynamic endpoint was plasma angiotensin-converting enzyme (ACE) activity. Benazeprilat data were fitted to an equation corresponding to a single-compartment model with a volume equal to the blood space (Vc = 0.093 L/kg). Within this space, Benazeprilat was bound nonlinearly to ACE, which was mainly tissular (89.4%) rather than circulating (10.6%). Free Benazeprilat was eliminated quickly from the central compartment (t1/2 approximately 1.0 h; Cl approximately 0.125 L/kg/h), elimination being principally biliary ( approximately 85%) rather than urinary ( approximately 15%). Nevertheless, inhibition of ACE was long-lasting (t1/2 16-23 h) due to high affinity binding of Benazeprilat to ACE (Kd approximately 3.5 mmol/L, IC50 approximately 4.3 mmol/L). Simulations using the model predict a lack of proportionality between dose of benazepril, plasma Benazeprilat concentrations and effect due to the nonlinear binding of Benazeprilat to ACE. For example, increasing the dose of benazepril (e.g. above 0.125 mg/kg q24 h) produced only small incremental inhibition of ACE (either peak effect or duration of action).