Pitavastatin lactone
(Synonyms: 匹伐他汀内酯) 目录号 : GC44650
A major phase 2 metabolite of pitavastatin
Cas No.:141750-63-2
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
Pitavastatin lactone is a major phase 2 metabolite of pitavastatin , an inhibitor of HMG-CoA reductase, that is found in plasma of rats and humans following oral administration., Pitavastatin lactone is formed when pitavastatin undergoes glucuronidation by the UDP-glucuronysyl transferases UGT1A1, UGT1A3, or UGT2B7 to form pitavastatin glucuronide, which then undergoes non-enzymatic conversion to pitavastatin lactone. It can be converted back to pitavastatin via hydrolysis.
| Cas No. | 141750-63-2 | SDF | |
| 别名 | 匹伐他汀内酯 | ||
| Canonical SMILES | FC(C=C1)=CC=C1C2=C(/C=C/[C@H]3OC(C[C@H](O)C3)=O)C(C4CC4)=NC5=C2C=CC=C5 | ||
| 分子式 | C25H22FNO3 | 分子量 | 403.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml,Ethanol: 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 | 2.4783 mL | 12.3916 mL | 24.7831 mL |
| 5 mM | 0.4957 mL | 2.4783 mL | 4.9566 mL |
| 10 mM | 0.2478 mL | 1.2392 mL | 2.4783 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。
Simple LC-MS/MS methods for simultaneous determination of pitavastatin and its lactone metabolite in human plasma and urine involving a procedure for inhibiting the conversion of Pitavastatin lactone to pitavastatin in plasma and its application to a pharmacokinetic study
J Pharm Biomed Anal 2013 Jan;72:8-15.PMID:23146221DOI:10.1016/j.jpba.2012.09.026.
Sometimes, drugs and their metabolites in plasma may convert to each other. This phenomenon is called interconversion, which may result in the instability problem of the plasma samples. The instability problem caused by interconversion of the co-existing metabolites may often be ignored, since there is no drug metabolite in the quality control samples prepared for method validation. Pitavastatin lactone (Pi-LAC), a main metabolite of pitavastatin (Pi), is very unstable and easily converted to Pi in plasma. In this paper, simple and rapid LC-ESI-MS/MS methods were developed for the simultaneous determination of Pi and Pi-LAC in human plasma and urine. The sample stability was examined under different conditions. The interconversion of Pi and Pi-LAC was prevented by adding a pH 4.2 buffer solution to the freshly collected plasma samples. Detection was performed using an electrospray ionization (ESI) operating in positive ion multiple reaction monitoring mode by monitoring the ion transitions from m/z 422.2→290.3 (Pi), 404.2→290.3 (Pi-LAC) and m/z 611.3→423.2 (candesartan cilextetil, the internal standard), respectively. The calibration curve of Pi and Pi-LAC in both human plasma and urine showed good linearity over the concentration range of 0.1-200 ng/mL. The established methods were successfully applied to a pharmacokinetic study of pitavastatin calcium tablets in healthy Chinese volunteers after oral administration of 1, 2 and 4 mg single and multiple doses of pitavastatin calcium. The pharmacokinetic parameters of Pi and Pi-LAC in Chinese volunteers were given respectively. The urinary excretion profiles of Pi and Pi-LAC in Chinese volunteers were also presented. After receiving a single 4 mg oral dose of pitavastatin calcium, the average cumulative urinary excretion percentages of Pi and Pi-LAC in Chinese volunteers were (0.41 ± 0.16)% and (6.1 ± 5.0)%, respectively.
Pitavastatin - pharmacological profile from early phase studies
Atheroscler Suppl 2010 Dec;11(3):3-7.PMID:21193152DOI:10.1016/S1567-5688(10)71063-1.
Pitavastatin has been designed as a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor with a novel cyclopropyl moiety that results in several differences compared to other statins. These include effective inhibition of cholesterol synthesis and increased lipoprotein lipase expression at lower doses than other statins, and significant high-density lipoprotein-cholesterol and apolipoprotein A1-elevating activity that persists with time. The safety, tolerability and pharmacokinetics of pitavastatin and its major metabolite, Pitavastatin lactone, have been investigated in a variety of patient groups with similar results, which suggests dosage adjustments are not required for gender, age or race. In healthy subjects, pitavastatin is well tolerated at the approved doses with no serious adverse events. The bioavailability of pitavastatin is, at 60%, higher than that of any other statin and the majority of the bioavailable fraction of an oral dose is excreted unchanged in the bile. The entero-hepatic circulation of unchanged drug contributes to the prolonged duration of action and allows once-daily, any-time dosing. Pitavastatin is only slightly metabolised by cytochrome P450 (CYP) 2C9 and not at all by CYP3A4. Neither pitavastatin nor its lactone form, have inhibitory effects on CYP, and CYP3A4 inhibitors have no effect on pitavastatin concentrations. Moreover, P-glycoprotein-mediated transport does not play a major role in the drug's disposition and pitavastatin does not inhibit P-glycoprotein activity. Pitavastatin is transported into the liver by several hepatic transporters but OATP1B1 inhibitors have relatively little effect on plasma concentrations compared with other statins. In general, interactions, except with multi-transporter inhibitors like ciclosporin, are not clinically significant. Consequently, pitavastatin has minimal drug-food and drug-drug interactions making it a treatment option in the large group of dyslipidaemic people that require multidrug therapy.