| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| ln Vitro |
The paper mentions that Atorvastatin lactone and the lactones of hydroxy metabolites are converted to their corresponding acid forms via base hydrolysis, and these acids are quantified if they demonstrate HMG-CoA reductase inhibitory activity. This implies that Atorvastatin lactone itself may not be an active inhibitor but becomes one upon hydrolysis. [1]
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| Enzyme Assay |
It is a component measured within a larger HMG-CoA reductase inhibition assay protocol. In this protocol, for the determination of "total" inhibitor concentration, plasma samples are treated with potassium hydroxide (0.5 N) to hydrolyze Atorvastatin lactone and other lactones to their acid forms. After pH adjustment, the resulting acids are then measured via their ability to inhibit HMG-CoA reductase in the enzyme assay. [1]
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| ADME/Pharmacokinetics |
It is mentioned that in clinical studies, the areas under the concentration-time curves (AUCs) of the lactone and the acid forms of atorvastatin were determined to be similar. Consequently, using the enzyme inhibition assay approach, the concentrations of 'total' HMG-CoA reductase inhibitors (which include acids derived from lactones after hydrolysis) and their AUCs would be approximately twice that of the concentration and AUCs of the 'active' inhibitors (atorvastatin acid and its hydroxy acid metabolites).
A representative plasma concentration profile is shown (Fig. 6), illustrating that post-dose concentrations obtained for the 'total' inhibitors (which include the contribution from hydrolyzed lactone) are close to double the concentrations of the 'active inhibitors'. The assay method ensures chemical stability of Atorvastatin lactone during sample preparation by thawing samples in an ice-water bath, centrifuging at 4°C, and adding acetic acid to adjust the pH to approximately 7, minimizing unwanted in-situ hydrolysis. [1] |
| References | |
| Additional Infomation |
Atorvastatin lactone is a metabolite of atorvastatin, a synthetic inhibitor of HMG-CoA reductase used to treat hypercholesterolemia. In the context of this paper, it is an important analyte for determining the "total" HMG-CoA reductase inhibitory activity in human plasma following atorvastatin administration.
The analytical method described is an automated enzyme inhibition assay that measures atorvastatin-derived HMG-CoA reductase inhibitors. The "active" inhibitor concentration refers to the inhibitory activity of atorvastatin (acid) and its hydroxy acid metabolites. The "total" inhibitor concentration is measured after base hydrolysis of the plasma sample. This hydrolysis step converts Atorvastatin lactone and the lactones of the hydroxy metabolites back to their corresponding acid forms, which are then capable of inhibiting the enzyme. The difference between the 'total' and 'active' concentrations provides an indication of the concentration of lactone species present in the sample. [1] |
| Exact Mass |
540.242
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|---|---|
| CAS # |
125995-03-1
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| Related CAS # |
Atorvastatin lactone-d5
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| PubChem CID |
6483036
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| Appearance |
White to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
674.8±55.0 °C at 760 mmHg
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| Melting Point |
103-106ºC
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| Flash Point |
361.9±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.617
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
40
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| Complexity |
834
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C(C1=C(C(C)C)N(CC[C@@H]2C[C@@H](O)CC(O2)=O)C(C3=CC=C(F)C=C3)=C1C4=CC=CC=C4)NC5=CC=CC=C5
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| InChi Key |
OUCSEDFVYPBLLF-KAYWLYCHSA-N
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| InChi Code |
InChI=1S/C33H33FN2O4/c1-21(2)31-30(33(39)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-27-19-26(37)20-28(38)40-27/h3-16,21,26-27,37H,17-20H2,1-2H3,(H,35,39)/t26-,27-/m1/s1
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| Chemical Name |
5-(4-fluorophenyl)-1-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-N,4-diphenyl-2-propan-2-ylpyrrole-3-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
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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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~46.24 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00414531 | COMPLETED | Drug: Atorvastatin | Myotoxicity of Atorvastatin Treatment | University of Oslo School of Pharmacy | 2005-05 | Phase 4 |
| NCT03604471 | COMPLETED | Drug: Atorvastatin | Hypercholesterolemia | Université Catholique de Louvain | 2017-08-08 | Phase 4 |
| NCT03311841 | COMPLETEDWITH RESULTS | Drug: Midazolam oral solution Drug: Dabigatran and pitavastatin oral solution Drug: Atorvastatin and rosuvastatin oral solution Drug: Rifampin |
Renal Insufficiency | Merck Sharp & Dohme LLC | 2018-03-01 | Phase 1 |
| NCT05334108 | COMPLETED | Drug: Ecopipam Combination Product: Cohort 1 Probe Substrate Cocktail Drug: Cohort 2 Probe Substrate Combination Product: Cohort 3 Probe Substrate Cocktail |
Drug Interaction | Emalex Biosciences Inc. | 2022-04-26 | Phase 1 |
| NCT04764851 | TERMINATED | Drug: ecopipam HCl ~2mg/kg/day Combination Product: Cohort 1 Probe Cocktail Combination Product: Cohort 2 Probe Cocktail Combination Product: Cohort 3 Probe Cocktail |
Drug-Interactions | Emalex Biosciences Inc. | 2021-02-18 | Phase 1 |
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