Atorvastatin (calcium salt hydrate)
目录号 : GC46889
An HMG-CoA reductase inhibitor
Cas No.:357164-38-6
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
Atorvastatin is an inhibitor of HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway of cholesterol synthesis, that has IC50 values of 73, 102, and 0.6 nM for HepG2 cells, human fibroblasts, and rat hepatocytes, respectively.1 Formulations containing atorvastatin have been used in the treatment of hypercholesterolemia and certain dyslipidemias.
1.Shaw, M.K., Newton, R.S., Sliskovic, D.R., et al.Hep-G2 cells and primary rat hepatocytes differ in their response to inhibitors of HMG-CoA reductaseBiochem. Biophys. Res. Commun.170(2)726-734(1990)
| Cas No. | 357164-38-6 | SDF | |
| Canonical SMILES | O=C(C1=C(C(C)C)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C2=CC=C(F)C=C2)=C1C3=CC=CC=C3)NC4=CC=CC=C4.O=C(C5=C(C(C)C)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C6=CC=C(F)C=C6)=C5C7=CC=CC=C7)NC8=CC=CC=C8.[Ca+2].O | ||
| 分子式 | C33H34FN2O5.1/2Ca [XH2O] | 分子量 | 577.7 |
| 溶解度 | DMF: 25 mg/ml,DMF:PBS (pH 7.2) (1:9): 0.1 mg/ml,DMSO: 15 mg/ml,Ethanol: 0.5 mg/ml | 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 | 1.731 mL | 8.655 mL | 17.31 mL |
| 5 mM | 0.3462 mL | 1.731 mL | 3.462 mL |
| 10 mM | 0.1731 mL | 0.8655 mL | 1.731 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。
Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor
Clin Pharmacokinet 2017 Dec;56(12):1461-1478.PMID:28417439DOI:10.1007/s40262-017-0543-3.
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a two-fold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1.9-fold for sacubitrilat, and ~1.7-fold for valsartan in healthy subjects. Following multiple twice-daily administration, steady-state maximum plasma concentration was reached within 3 days, showing no accumulation for sacubitril and valsartan, while ~1.6-fold accumulation for sacubitrilat. Sacubitril is eliminated predominantly as sacubitrilat through the kidney; valsartan is eliminated mainly by biliary route. Drug-drug interactions of sacubitril/valsartan were evaluated with medications commonly used in patients with heart failure including furosemide, warfarin, digoxin, carvedilol, levonorgestrel/ethinyl estradiol combination, amlodipine, omeprazole, hydrochlorothiazide, intravenous nitrates, metformin, statins, and sildenafil. Co-administration with sacubitril/valsartan increased the maximum plasma concentration (~2.0-fold) and area under the plasma concentration-time curve (1.3-fold) of Atorvastatin; however, it did not affect the pharmacokinetics of simvastatin. Age, sex, or ethnicity did not affect the pharmacokinetics of sacubitril/valsartan. In patients with heart failure vs. healthy subjects, area under the plasma concentration-time curves of sacubitril, sacubitrilat, and valsartan were higher by approximately 1.6-, 2.1-, and 2.3-fold, respectively. Renal impairment had no significant impact on sacubitril and valsartan area under the plasma concentration-time curves, while the area under the plasma concentration-time curve of sacubitrilat correlated with degree of renal function (1.3-, 2.3-, 2.9-, and 3.3-fold with mild, moderate, and severe renal impairment, and end-stage renal disease, respectively). Moderate hepatic impairment increased the area under the plasma concentration-time curves of valsartan and sacubitrilat ~2.1-fold.
Does the trihydrate of Atorvastatin calcium possess a melting point?
Eur J Pharm Sci 2020 May 30;148:105334.PMID:32259678DOI:10.1016/j.ejps.2020.105334.
To decide whether an active pharmaceutical ingredient can be used in its amorphous form in drug formulations, often the glass transition is studied in relation to the melting point of the pharmaceutical. If the glass transition temperature is high enough and found relatively close to the melting point, the pharmaceutical is considered to be a good glass former. However, it is obviously important that the observed melting point and glass transition involve exactly the same system, otherwise the two temperatures cannot be compared. Although this may seem trivial, in the case of hydrates, where water may leave the system on heating, the composition of the system may not be evident. Atorvastatin calcium is a case in point, where confusing terminology, absence of a proper anhydrate form, and loss of water on heating lead to several doubtful conclusions in the literature. However, considering that no anhydrate crystal has ever been observed and that the glass transition of the anhydrous system is found at 144 °C, it can be concluded that if the system is kept isolated from water, the chances that Atorvastatin calcium crystallises at room temperature is negligible. The paper discusses the various thermal effects of Atorvastatin calcium on heating and proposes a tentative binary phase diagram with water.
Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of Atorvastatin using multivariate data analysis
Pharm Res 2013 Mar;30(3):826-35.PMID:23138263DOI:10.1007/s11095-012-0923-1.
Purpose: To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of Atorvastatin. Methods: Multivariate curve resolution (MCR) was used to decompose a variable-temperature synchrotron X-ray powder diffraction (VT-XRPD) data matrix into diffraction patterns and concentration profiles of pure drug phases. Results: By means of the MCR-estimated diffraction patterns and concentration profiles, the trihydrate phase of the drug salt was found to dehydrate sequentially into two partially dehydrated hydrate structures upon heating from 25 to 110°C, with no associated breakage of the original crystal lattice. During heating from 110 to 140°C, the remaining water was lost from the solid drug salt, which instantly collapsed into a liquid crystalline phase. An isotropic melt was formed above 155°C. Thermogravimetric analysis, hot-stage polarized light microscopy, and hot-stage Raman spectroscopy combined with principal component analysis (PCA) was shown to provide consistent results. Conclusions: This study demonstrates that MCR combined with VT-XRPD is a powerful tool for rapid interpretation of complex dehydration behavior of drug hydrates, and it is also the first report on a liquid crystalline phase of the calcium salt of Atorvastatin.
Formulation, and optimization of transdermal Atorvastatin Calcium-Loaded Ultra-flexible vesicles; ameliorates poloxamer 407-caused dyslipidemia
Int J Pharm 2023 May 10;638:122917.PMID:37019321DOI:10.1016/j.ijpharm.2023.122917.
Atorvastatin calcium (AC), a cholesterol-lowering medication, has limited oral bioavailability (14 %) and adverse impacts on the gastrointestinal tract (GIT), liver, and muscle. So, in an effort to improve the poor availability and overcome the hepatotoxicity complications attendant to peroral AC administration, transdermal transfersomal gel (AC-TFG) was developed as a convenient alternative delivery technique. The impact of utilizing an edge activator (EA) and varying the phosphatidylcholine (PC): EA molar ratio on the physico-chemical characteristics of the vesicles was optimized through a Quality by Design (QbD) strategy. The optimal transdermal AC-TFG was tested in an ex-vivo permeation study employing full-thickness rat skin, Franz cell experiments, an in-vivo pharmacokinetics and pharmacodynamics (PK/PD) evaluation, and a comparison to oral AC using poloxamer-induced dyslipidemic Wister rats. The optimized AC-loaded TF nanovesicles predicted by the 23-factorial design strategy had a good correlation with the measured vesicle diameter of 71.72 ± 1.159 nm, encapsulation efficiency of 89.13 ± 0.125 %, and cumulative drug release of 88.92 ± 3.78 % over 24 h. Ex-vivo data revealed that AC-TF outperformed a free drug in terms of permeation. The pharmacokinetic parameters of optimized AC-TFG demonstrated 2.5- and 13.3-fold significant improvements in bioavailability in comparison to oral AC suspension (AC-OS) and traditional gel (AC-TG), respectively. The transdermal vesicular technique preserved the antihyperlipidemic activity of AC-OS without increasing hepatic markers. Such enhancement was proven histologically by preventing the hepatocellular harm inflicted by statins. The results showed that the transdermal vesicular system is a safe alternative way to treat dyslipidemia with AC, especially when given over a long period of time.
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2010 Jul-Aug;32(6):437-61.PMID:20852754DOI:10.1358/mf.2010.32.6.1538165.
A-3309, Abobotulinumtoxin A, Adalimumab, AIDSVAX gp120 B/E, ALVAC E120TMG, Atorvastatin calcium; Bepridil, Bevacizumab; Candesartan cilexetil, Capecitabine, Cetuximab, Clopidogrel; Dapagliflozin, Dasatinib, Denosumab, Dexmedetomidine hydrochloride, Diacetylmorphine, Diannexin, Docetaxel, Dutasteride; Entecavir, Eplerenone, Erlotinib hydrochloride, Escitalopram oxalate, Everolimus, Ezetimibe; Fesoterodine fumarate, Flagellin.HuM2e, Fluzone; Glimepiride/rosiglitazone maleate; Hyaluronic acid-paclitaxel bioconjugate; IDX-184, Imatinib mesylate, Infliximab, Insulin glargine, Irbesartan; JX-594; Landiolol, Latrunculin B, Levocetirizine dihydrochloride, Liraglutide, Lyprinol; Metformin, Metronidazole/tetracycline hydrochloride/bismuth biskalcitrate, Mipomersen sodium, Mycophenolic acid sodium salt; Nalfurafine hydrochloride, Nilotinib hydrochloride monohydrate; Paclitaxel nanoparticles, Paclitaxel poliglumex, Peginterferon alfa-2a, Peginterferon alfa-2b, Perospirone hydrochloride, Pimavanserin tartrate, Pirfenidone, Pitavastatin calcium, Prasterone, Prasugrel, Pregabalin, Ranelic acid distrontium salt, Ranibizumab, Remimazolam, Risedronate, Rosuvastatin calcium; Silodosin, Silybin phosphatidylcholine complex, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sorafenib, Sunitinib malate; Tadalafil, Tamsulosin hydrochloride, Technosphere/insulin, Telmisartan, Temsirolimus, Teriparatide, Thymalfasin, Ticagrelor, Toltedorine-XR, Tramadol-XR, Triphosadenine, Trospium-XR; Val8-GLP-1(7-37)OH, Valsartan, Vardenafil hydrochloride hydrate, Varenicline tartrate, Velaglucerase alfa; Zoledronic acid monohydrate.