145599-86-6
145599-86-6 結(jié)構(gòu)式
基本信息
西立伐他汀鈉
西伐他汀
西立伐他汀
CERIVASTATIN NA
CERIVASTATIN SODIUM
CERIVASTATIN, SODIUM SALT
LIPOBAY
RIVASTATIN
sodium 7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-dipropan-2-yl-pyrid in-3-yl]-3,5-dihydroxy-hept-6-enoate
7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-dipropan-2-yl-pyrid in-3-yl]-3,5-dihydroxy-hept-6-enoate
(3R,5S,6E)-7-[4-(p-Fluorophenyl)-2,6-diisopropyl-5-(methoxymethyl)-3-pyridyl]-3,5-dihydroxy-6-heptenoic acid
6-Heptenoic acid, 7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-bis(1-methylethyl)-3-pyridinyl]-3,5-dihydroxy-, (3R,5S,6E)-
6-Heptenoic acid, 7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-bis(1-methylethyl)-3-pyridinyl]-3,5-dihydroxy-, [S-[R*,S*-(E)]]-
物理化學(xué)性質(zhì)
常見問題列表
西立伐他汀口服后吸收迅速而完全由于藥物和肝臟有高度親和力，所以大部分藥物停留在肝臟發(fā)揮作用，肝臟首次關(guān)卡效應(yīng)低。西立伐他汀的生物轉(zhuǎn)化主要發(fā)生在肝臟，藥物主要轉(zhuǎn)化為M1，M23和M24，且均有生理活性。一次口服西立伐他汀0.2mg，Cmax為2.98μg•L-1，Tmax為1～4h，AUC0～∞為14.19μg•L-1•h-1，T12為3.26h。藥物動(dòng)力學(xué)參數(shù)性別間無明顯差別[6]。34%藥物從腎臟排泄，其余藥物經(jīng)腸肝循環(huán)排泄。輕度腎功能不全時(shí)不需調(diào)整用藥劑量。西立伐他汀的一個(gè)顯著優(yōu)點(diǎn)是與其他藥物(如華法令、地高辛)在藥物動(dòng)力學(xué)方面無相互干擾。
西立伐他汀具有很好的調(diào)脂作用。觀察到西立伐他汀0.2mg•d-1應(yīng)用5wk后可使血清低密度脂蛋白膽固醇(LDL-C)降低30.5%。與此同時(shí)西立伐他汀可降低血清TC，TG，載脂蛋白B，升高血清高密度脂蛋白膽固醇(HDL-C)濃度。西立伐他汀0.025～0.4mg•d-1可使血清LDL-C明顯下降，下降幅度與藥物劑量成正相關(guān)。當(dāng)西立伐他汀劑量為0.4mg•d-1時(shí)，大于40%的病人血清LDL-C下降大于40%，9%病人血清LDL-C下降大于50%。在該劑量下血清TG明顯下降，而HDL-C、載脂蛋白 A-1明顯上升。對(duì)2593例使用西立伐他汀的病人進(jìn)行分析，對(duì)照組(520例)不用藥。療效統(tǒng)計(jì)均取8wk。
Ki: 1.3 nM/L (HMG-CoA reductase)
Cerivastatin (5-50 ng/mL; 3 days; MDA-MB-231 cells) treatment induces a dose-dependent decrease in cell proliferation of MDA-MB-231 cells (up to 40% inhibition at 25 ng/mL).
Cerivastatin (25 ng/mL; 18-36 hours; MDA-MB-231 cells) treatment induces an arrest of the cell cycle in G 1/S phase after 36 h treatment. This arrest is not observed for a shorter incubation time (18 h).
Cerivastatin (25 ng/mL; 18 hours; MDA-MB-231 cells) treatment induces a marked increase in the level of p21
Waf1/Cip1
.
Cerivastatin (25 ng/mL; 12 hours; MDA-MB-231 cells) treatment increases the p21 transcript in MDA-MB-231 cells.
Cerivastatin (10-25 ng/mL; 18 hours) inhibits invasion of MDA-MB-231 cells through Matrigel.
Cerivastatin (25 ng/mL; 18-36 hours) delocalizes RhoA and Ras from the membrane to the cytosol and induces morphological changes.
Cerivastatin (25 ng/mL; 4-36 hours) induces inactivation of NFκB, in a RhoA inhibition-dependent manner, resulting in a decrease in urokinase and metalloproteinase-9 expression, and concomitantly increases IκB.
Cell Proliferation Assay
| Cell Line: | MDA-MB-231 cells |
| Concentration: | 5 ng/mL, 10 ng/mL, 25 ng/mL, 50 ng/mL |
| Incubation Time: | 3 days |
| Result: | Induced a dose-dependent decrease in cell proliferation of MDA-MB-231 cells. |
Cell Cycle Analysis
| Cell Line: | MDA-MB-231 cells |
| Concentration: | 25 ng/mL |
| Incubation Time: | 18 hours, 36 hours |
| Result: | Induced a cell cycle block in G 1/S phase. |
Western Blot Analysis
| Cell Line: | MDA-MB-231 cells |
| Concentration: | 25 ng/mL |
| Incubation Time: | 18 hours |
| Result: | Induced a marked increase in the level of p21 Waf1/Cip1 . |
RT-PCR
| Cell Line: | MDA-MB-231 cells |
| Concentration: | 25 ng/mL |
| Incubation Time: | 12 hours |
| Result: | Increased p21 Waf1/Cip1 mRNA levels. |
Cerivastatin is well absorbed, reaching maximal plasma levels in 1-3 hours following oral dosing. In the circulation, Cerivastatin is highly bound to plasma proteins (99.5%), with an elimination half-life of 2-4 hours. Cerivastatin is metabolized predominantly in the liver to three polar metabolites. Two of these metabolites are active, but to a lesser extent compared to parent drug, and the third metabolite is inactive. Plasma concentrations of all metabolites are substantially lower than those of the parent drug. Elimination of metabolites is via the urine (20-25%) and feces (66-73%), while essentially no parent compound is excreted.