Pravastatin lactone
(Synonyms: 普伐他汀类酯) 目录号 : GC44676A metabolite of pravastatin
Cas No.:85956-22-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pravastatin lactone is a metabolite of pravastatin , a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that is a ring-hydroxylated metabolite of mevastatin . Pravastatin lactone is formed when pravastatin undergoes acid-catalyzed non-enzymatic lactonization in the stomach following oral administration.
| Cas No. | 85956-22-5 | SDF | |
| 别名 | 普伐他汀类酯 | ||
| Canonical SMILES | O=C([C@@H](C)CC)O[C@@H]1[C@@]2([H])C(C=C[C@H](C)[C@@H]2CC[C@@H]3C[C@@H](O)CC(O3)=O)=C[C@@H](O)C1 | ||
| 分子式 | C23H34O6 | 分子量 | 406.5 |
| 溶解度 | DMF: 25 mg/ml,DMSO: 20 mg/ml,Ethanol: 12.5 mg/ml,PBS (pH 7.2): 10 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.46 mL | 12.3001 mL | 24.6002 mL |
| 5 mM | 0.492 mL | 2.46 mL | 4.92 mL |
| 10 mM | 0.246 mL | 1.23 mL | 2.46 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。
Determination of pravastatin and Pravastatin lactone in rat plasma and urine using UHPLC-MS/MS and microextraction by packed sorbent
Talanta 2012 Feb 15;90:22-9.PMID:22340111DOI:10.1016/j.talanta.2011.12.043.
A simple and reproducible method for the determination of pravastatin and Pravastatin lactone in rat plasma and urine by means of ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) using deuterium labeled internal standards for quantification is reported. Separation of analytes was performed on BEH C(18) analytical column (50 mm × 2.1mm, 1.7 μm), using gradient elution by mobile phase consisting of acetonitrile and 1mM ammonium acetate at pH 4.0. Run time was 2 min. Quantification of analytes was performed using the SRM (selected reaction monitoring) experiment in ESI negative ion mode for pravastatin and in ESI positive ion mode for Pravastatin lactone. Sample treatment consisted of a protein precipitation by ACN and microextraction by packed sorbent (MEPS) for rat plasma. Simple MEPS procedure was sufficient for rat urine. MEPS was implemented using the C8 sorbent inserted into a microvolume syringe, eVol hand-held automated analytical syringe and a small volume of sample (50 μl). The analytes were eluted by 100 μl of the mixture of acetonitrile: 0.01 M ammonium acetate pH 4.5 (90:10, v:v). The method was validated and demonstrated good linearity in range 5-500 nmol/l (r(2)>0.9990) for plasma and urine samples. Method recovery was ranged within 97-109% for plasma samples and 92-101% for the urine samples. Intra-day precision expressed as the % of RSD was lower than 8% for the plasma samples and lower than 7% for the urine samples. The method was validated with sensitivity reaching LOD 1.5 nmol/l and LOQ 5 nmol/l in plasma and urine samples. The method was applied for the measurement of pharmacokinetic plots of pravastatin and Pravastatin lactone in rat plasma and urine samples.
Statin induced myotoxicity: the lactone forms are more potent than the acid forms in human skeletal muscle cells in vitro
Eur J Pharm Sci 2008 Apr 23;33(4-5):317-25.PMID:18294823DOI:10.1016/j.ejps.2007.12.009.
Statins exist in both acid and lactone forms in vivo. High plasma levels of the lactone forms have been observed in patients with statin induced myopathy. In the present study, the hypothesis that lactone forms have a higher potency of inducing myotoxicity as compared to acid forms was investigated. Primary human skeletal muscle cells were incubated with increasing concentrations of lactone and acid forms of atorvastatin, fluvastatin, pravastatin and simvastatin. Following incubation, living myotubes were quantified by fluorescence staining. Atorvastatin lactone showed a 14-fold, fluvastatin lactone a 26-fold, Pravastatin lactone a 23-fold, and simvastatin lactone a 37-fold higher potency to induce myotoxicity compared to their corresponding acid forms. Thus, for the four different statins the present study shows a significantly higher potency of the lactone forms, than the respective acid forms, to induce myotoxicity in human skeletal muscle cells in vitro. These results clearly indicate the need to differentiate between acid and lactone forms in future investigation of statin myotoxicity.
The role of acid-base imbalance in statin-induced myotoxicity
Transl Res 2016 Aug;174:140-160.e14.PMID:27083388DOI:10.1016/j.trsl.2016.03.015.
Disturbances in acid-base balance, such as acidosis and alkalosis, have potential to alter the pharmacologic and toxicologic outcomes of statin therapy. Statins are commonly prescribed for elderly patients who have multiple comorbidities such as diabetes mellitus, cardiovascular, and renal diseases. These patients are at risk of developing acid-base imbalance. In the present study, the effect of disturbances in acid-base balance on the interconversion of simvastatin and pravastatin between lactone and hydroxy acid forms have been investigated in physiological buffers, human plasma, and cell culture medium over pH ranging from 6.8-7.8. The effects of such interconversion on cellular uptake and myotoxicity of statins were assessed in vitro using C2C12 skeletal muscle cells under conditions relevant to acidosis, alkalosis, and physiological pH. Results indicate that the conversion of the lactone forms of simvastatin and pravastatin to the corresponding hydroxy acid is strongly pH dependent. At physiological and alkaline pH, substantial proportions of simvastatin lactone (SVL; ∼87% and 99%, respectively) and Pravastatin lactone (PVL; ∼98% and 99%, respectively) were converted to the active hydroxy acid forms after 24 hours of incubation at 37°C. At acidic pH, conversion occurs to a lower extent, resulting in greater proportion of statin remaining in the more lipophilic lactone form. However, pH alteration did not influence the conversion of the hydroxy acid forms of simvastatin and pravastatin to the corresponding lactones. Furthermore, acidosis has been shown to hinder the metabolism of the lactone form of statins by inhibiting hepatic microsomal enzyme activities. Lipophilic SVL was found to be more cytotoxic to undifferentiated and differentiated skeletal muscle cells compared with more hydrophilic simvastatin hydroxy acid, PVL, and pravastatin hydroxy acid. Enhanced cytotoxicity of statins was observed under acidic conditions and is attributed to increased cellular uptake of the more lipophilic lactone or unionized hydroxy acid form. Consequently, our results suggest that comorbidities associated with acid-base imbalance can play a substantial role in the development and potentiation of statin-induced myotoxicity.
Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese
Br J Clin Pharmacol 2004 Apr;57(4):448-55.PMID:15025743DOI:10.1046/j.1365-2125.2003.02030.x.
Aims: To investigate the effects of repeated grapefruit juice (GFJ) intake on the pharmacokinetics of atorvastatin and pravastatin in Japanese subjects. Methods: Two randomized, two-way crossover studies were performed. GFJ or water was given to two groups of 10 subjects each three times daily for 2 days. On the third day, single 10 mg doses of atorvastatin or pravastatin were orally administered with GFJ or water, and an additional 250 ml of GFJ or water was taken before lunch and dinner. Plasma concentrations of atorvastatin and its metabolites were determined over 48 h postdosing and of pravastatin and its metabolites over 24 h postdosing. Results: Compared with in the water group, the AUC(0,48 h) of atorvastatin acid significantly increased by 1.40 fold (95% CI 1.02, 1.92; P < 0.05) when atorvastatin was taken with GFJ. AUC(0,48 h) and C(max) of atorvastatin lactone significantly increased by 1.56 (95% CI 1.33, 1.83; P < 0.001) and 1.29 fold (95% CI 1.09, 1.51; P < 0.01), respectively, when atorvastatin was taken with GFJ. No significant changes were detected in any pravastatin pharmacokinetic parameter examined when pravastatin was taken with GFJ. However, AUC(0,24 h) of Pravastatin lactone increased 1.31 fold (95% CI 1.01, 1.71; P < 0.05) with GFJ intake. Conclusions: GFJ was confirmed to significantly affect the pharmacokinetics of atorvastatin but had little or no effect on those of pravastatin in Japanese subjects.
Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin
Clin Pharmacol Ther 1999 Aug;66(2):118-27.PMID:10460065DOI:10.1053/cp.1999.v66.100453001.
Background: Grapefruit juice greatly increases the bioavailability of lovastatin and simvastatin. We studied the effect of grapefruit juice on the pharmacokinetics of atorvastatin and pravastatin. Methods: Two randomized, two-phase crossover studies were performed--study I with atorvastatin in 12 healthy volunteers and study II with pravastatin in 11 healthy volunteers. In both studies, volunteers took 200 mL double-strength grapefruit juice or water three times a day for 2 days. On day 3, each subject ingested a single 40 mg dose of atorvastatin (study I) or pravastatin (study II) with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 hour and 1 1/2 hours later. In addition, subjects took 200 mL grapefruit juice or water three times a day on days 4 and 5 in study I. In study I, serum concentrations of atorvastatin acid, atorvastatin lactone, 2-hydroxyatorvastatin acid, 2-hydroxyatorvastatin lactone, and active and total 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors were measured up to 72 hours. In study II, pravastatin, Pravastatin lactone, and active and total HMG-CoA reductase inhibitors were measured up to 24 hours. Results: Grapefruit juice increased the area under the serum concentration-time curve of atorvastatin acid from time zero to 72 hours [AUC(0-72)] 2.5-fold (P < .01), whereas the peak serum concentration (Cmax) was not significantly changed. The time of the peak concentration (tmax) and the elimination half-life (t1/2) of atorvastatin acid were increased (P < .01). The AUC(0-72) of atorvastatin lactone was increased 3.3-fold (P < .01) and the Cmax 2.6-fold (P < .01) by grapefruit juice, and the tmax and t1/2 were also increased (P < .05). Grapefruit juice decreased the Cmax (P < .001) and AUC(0-72) (P < .001) of 2-hydroxyatorvastatin acid and increased its tmax and t1/2 (P < .01). Grapefruit juice also decreased the Cmax (P < .001) and AUC(O-72) (P < .05) of 2-hydroxyatorvastatin lactone. The AUC(0-72) values of active and total HMG-CoA reductase inhibitors were increased 1.3-fold (P < .05) and 1.5-fold (P < .01), respectively, by grapefruit juice. In study II, the only significant change observed in the pharmacokinetics of pravastatin was prolongation of the tmax of active HMG-CoA reductase inhibitors by grapefruit juice (P < .05). Conclusions: Grapefruit juice significantly increased serum concentrations of atorvastatin acid, atorvastatin lactone, and active and total HMG-CoA reductase inhibitors, probably by decreasing CYP3A4-mediated first-pass metabolism of atorvastatin in the small intestine. On the other hand, grapefruit juice had no effect on the pharmacokinetics of pravastatin. Concomitant use of atorvastatin and at least large amounts of grapefruit juice should be avoided, or the dose of atorvastatin should be reduced accordingly.