The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin pharmacokinetics.In addition,we compared the fluvastatin pharmacokinetics differences between extended-release(ER)8...The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin pharmacokinetics.In addition,we compared the fluvastatin pharmacokinetics differences between extended-release(ER)80 mg tablet and immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter genetic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study(n=24),effects of ABCG2,SLCO1B1,ABCB1,CYP2C9 and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed.The administration dosage for IR 40 mg and ER 80 mg were twice and once daily,respectively,for total 7 d.Blood samples for pharmacokinetic evaluation were taken on the 1st and 7th d.The lower exposure following ER was observed.For ER tablets,SLCO1B1 T521C genotype correlated with AUC 0-24 of repeat doses(P=0.010).SLCO1B1 T521C genotype had no statistically significant effect on AUC 0-24 of IR capsule of fluvastatin after single or repeated doses.In vitro study demonstrated that when the concentration of fluvastatin was low(<1μmol/l),the uptake of fluvastatin in the HEK293-OATP1B1 with SLCO1B1521TT(K m=0.18μmol/l)was faster than that with SLCO1B1521CC(K m=0.49μmol/l),On the other hand,when concentration reached to higher level(>1μmol/l),transport velocity of fluvastatin by HEK293-OATP1B1 with SLCO1B1521TT(K m=11.4μmol/l)and with SLCO1B1521TCC(K m=15.1μmol/l)tend to be the same.It suggests that the increased effect of SLCO1B1 T521C genotype on ER formulation of fluvastatin was mainly caused by lower blood concentrations.We recommend that formulation should be incorporated into future pharmacogenomics studies.展开更多
The anti atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Method...The anti atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods.Fifty six rabbits were randomly divided into eight groups(n=7,each).Fluvastatin was given mixed with food at daily dose of8mg/kg starting 5 days before catheterization.Light microscope,immunohistochemistry,transmission electron microscope and RT PCR assay were applied to assess vascular smooth muscle cell (VSMC)proliferation and apoptosis, as well as oncogene expression in vascular wall. Results.At day 10 and day 15 after catheter induced denudation intima/media(I/M)thickness ratio was obviously higher, and also the percentage of PCNA positive cells and TUNEL positive cells in media was significantly higher compared with controls.The intimal hyperplasia was mostly composed of α SM actin positive cells.In rabbits given fluvastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvastatin.The overexpression of proto oncogene H ras mRNA and decreased expression of anti oncogene p53 mRNA were found after vascular injury,whereas fluvastatin significantly reduced H ras mRNA and increased p53 mRNA expression. Conclusion.Proliferation of VSMC in the media and the migration to the intima can be inhibited,and apoptosis of VSMC be induced by short term use of fluvastatin after balloon catheter denudation,independent of serum lipid change.The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.展开更多
Objective To study the protective effect of fluvastatin,one of the HMG-CoA reductase inhibitors (statins),against oxygen radical-induced oxidative damages in human aortic endothelial cell,and the role of Bcl-2 in this...Objective To study the protective effect of fluvastatin,one of the HMG-CoA reductase inhibitors (statins),against oxygen radical-induced oxidative damages in human aortic endothelial cell,and the role of Bcl-2 in this protection.Methods Human aortic endothelial cells with or without Bcl-2 siRNA transfection were subjected to 1-100 nM of fluvastatin and 100 la hydrogen peroxide for 24 hours.Bcl-2 mRNA and protein expression were measured by Taqman quantitative PCR and Western blotting.Cell apoptosis was measured by normal and fluorescent microscopy and Cell Death Detection ELISA.Results In the Bcl-2-expressed cells,fluvastatin significantly reversed hydrogen peroxide-induced microscopic apoptosis and apoptotic DNA fragmentation,which were accompanied by a markedly upregulation of Bcl-2 expression by fluvastatin.However,the endothelial protection by fluvastatin was completely lost in Bcl-2 siRNA transfected cells.Conclusion Fluvastatin protects human endothelial cells against oxygen radical-induced cell apoptosis in vitro,and this protection seemed to be mediated in a Bcl-2 dependent pathway.(J Geriatr Cardil 12008;5:33-38)展开更多
Objective: To investigate the effects of fluvastatin combined with β-receptor-blockers on cardiac function and peripheral blood NF-κB and sST2 in patients with coronary heart disease (CHD) complicated with heart fai...Objective: To investigate the effects of fluvastatin combined with β-receptor-blockers on cardiac function and peripheral blood NF-κB and sST2 in patients with coronary heart disease (CHD) complicated with heart failure. Methods: A total of 90 CHD patients complicated with heart failure from September 2016 to September 2017 were selected and randomly divided into the control group and the observation group, with 45 cases in each group. The control group was treated with arotinolol and the observation group was treated with arotinolol combined with fluvastatin. The clinical efficacy of the two groups after treatment was compared. The cardiac function index, blood lipid index, inflammatory factor and serum NF-κB and sST2 levels were detected and compared between the two groups. Results: The effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the cardiac function indexes of the two groups were significantly improved (P<0.05). The LVEF and LVFS of the observation group were significantly higher than those of the control group, and LVEDD and LVESD of the observation group were significantly lower those of the control group (P<0.05). The serum lipid index and inflammatory factors of the two groups were significantly decreased after treatment. The hs-CRP, TNF-α, TC and LDL-C of the observation group were significantly lower than those of the control group after treatment (P<0.05). After treatment, the serum NF-κB and sST2 were significantly decreased in both groups, and the serum NF-κB and sST2 in the observation group were significantly lower than those in the control group. There was no significant difference in the incidence of adverse reactions between the two groups (P<0.05). Conclusions: Fluvastatin combined with β-receptor-blockers can reduce the level of blood lipid and inflammatory factors more effectively and improve the clinical efficacy of the CHD patients complicated with heart failure. It can effectively reduce serum NF-κB and sST2 more effectively and improve prognosis.展开更多
AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs)cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. ...AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs)cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors on the ulceration in small intestines of rats.METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method.RESULTS: Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin)did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others(pravastatin, atorvastatin).CONCLUSION: Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.展开更多
The effects of NO-Fluvastatin on proliferation of human lens epithelial cells (HLECs) and the action mechanism were investigated. Cell proliferation was assessed by MTT assay. Cell cycle was analyzed by flow cytometry...The effects of NO-Fluvastatin on proliferation of human lens epithelial cells (HLECs) and the action mechanism were investigated. Cell proliferation was assessed by MTT assay. Cell cycle was analyzed by flow cytometry. The expression of cell cycle regulatory proteins CyclinE mRNA and P21waf1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). MTT staining colorimetry showed that HLECs proliferation was markedly inhibited by NO-Fluvastatin and the effect was dependently related to time (24, 48 and 72 h) and dosage (1, 5 and 20 μmol/L). Flow cytometry revealed that NO-Fluvastatin could significantly block HLECs in the G0/G1 phase, resulting in the increased cells in the G0/G1 phase and decreased in the S phase (P<0.05). RT-PCR showed that NO-Fluvastatin could obviously inhibit the CyclinE mRNA expression and induce the P21waf1 mRNA expression as compared with the negative control groups (P<0.05). This experiment suggested that NO-Fluvastatin could suppress the proliferation of HLECs by regulating cell cycle regulatory proteins (inhibiting the expression of CyclinE mRNA and inducing the expression of P21waf1 mRNA), resulting in the arrest of HLECs in the G0/G1 phase, which can offer theory basis for NO-Fluvastatin in treating posterior capsular opacification in clinic practice.展开更多
The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulation ...The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulation by fluvastatin were also investigated. 24 male Wistar rats were randomly divided into normal control group (n=8), diabetic nephropathy group (n=8) and fluvastatin-treated diabetic nephropathy group (15 mg/kg/d, n=8). The metabolic parameters were measured at the 8th week. The expression of transforming growth factor β 1 (TGF-β 1) and fibronectin (FN) was immunohistochemically examined. The expression of SGK1 was detected by RT-PCR and Western blot, and CTGF mRNA was assessed by RT-PCR. As compared to DN, blood glucose, 24-h urinary protein, Cer and kidney weight index were all decreased and the weight was increased obviously in group F. At the same time, mesangial cells and extracellular matrix proliferation were relieved significantly. The levels of cortex SGK1 mRNA and protein were up-regulated, and both TGF-β 1 and FN were down-regulated by fluvastatin. The mRNA of SGK1 was positively correlated with the CTGF, TGF-β 1 and FN. SGK1 expression is markedly up-regulated in the renal cortex of DN group and plays an important role in the development and progress of diabetic nephropathy by means of signal transduction. Fluvastatin suppressed the increased SGK1mRNA expression in renal cortex and postponed the development of diabetic nephropathy.展开更多
OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokine...OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release(ER) 80 mg tablet and an immediate-release(IR) 40 mg capsule in terms of drug metabolism enzyme and transporter ge.netic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study,ef.fects of BCRP,SLCO1B1,MDR1,CYP2C9,and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using highperformance liquid chromatography-tandem mass spectrometry.RESULTS The SLCO1 B1 T521 C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1 B1 T521 C genotype correlated with the AUC_(0-24) of repeat doses(P=0.01).The CYP2C9*3 genotype correlated with the AUC_(0-24) after the first dose IR40 mg capsule(P<0.05);however,the difference between CYP2C9*1/*1 and CYP2 C9*1/*3 was not statistically significant after repeated doses.CONCLUSION The effect of SLCO1B1T521C on fluvas.tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.展开更多
Most reported fluorescent probes have limitations in practical applications in living systems due to the strong autofluorescence background,construction of probes with near-infrared(NIR) fluorescence emission is an ac...Most reported fluorescent probes have limitations in practical applications in living systems due to the strong autofluorescence background,construction of probes with near-infrared(NIR) fluorescence emission is an accessible approach for addressing this challenge.We here designed a NIR fluorescent probe for monitoring the endogenous production of H_2S in living cells.The designed probe showed significant NIR fluorescence turn-on response to H_2S with high selectivity,enabling the sensitive detection H_2S.Importantly,the probe could be applied in monitoring the endogenous production of H_2S in raw 264.7 macrophages.This study showed that fluvastatin can promote the activity of cystathionineγ-lyase(CSE) for generation H_2S.展开更多
Multiple studies have investigated the associations between fluvatatin and the risk of breast cancer(BC),but their results were conflicting.A meta-analysis of observational studies published regarding this subject was...Multiple studies have investigated the associations between fluvatatin and the risk of breast cancer(BC),but their results were conflicting.A meta-analysis of observational studies published regarding this subject was conducted in the present study.It aims to estimate the associations between fluvastatin use and the risk of BC.Pubmed and chinese national knowledge infrastructure(CNKI) database was searched up to January,2015 to identify eligible observational studies,and the Newcastle-Ottawa Scale(NOS) was used to assess quality of the studies.Pooled relative risk(RR) estimates and 95% confidence intervals(CIs) were calculated(fixed effect model:Mantel-Haenszel).Heterogeneities were evaluated before the calculation.A sensitivity analysis was also conducted.In total,four studies contributed to the analysis.Overall,fluvastatin use negatively correlated with BC risk(RR = 0.74,95 % CI = 0.58,0.95).In conclusion,fluvastatin use may reduce the risk of BC,but more research is needed to confirm this finding.展开更多
基金This study was supported by grants from the National Key R&D Program of China(No.2016YFC0904900)National Natural Science Foundation(No.81673509 and No.81573504)of China+1 种基金Natural Science Foundation of Beijing Municipality(No.7171012)National Science and Technology Major Projects for“Major New Drugs Innovation and Development”of China(No.2017ZX09304028 and No.2017ZX09101001).
文摘The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin pharmacokinetics.In addition,we compared the fluvastatin pharmacokinetics differences between extended-release(ER)80 mg tablet and immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter genetic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study(n=24),effects of ABCG2,SLCO1B1,ABCB1,CYP2C9 and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed.The administration dosage for IR 40 mg and ER 80 mg were twice and once daily,respectively,for total 7 d.Blood samples for pharmacokinetic evaluation were taken on the 1st and 7th d.The lower exposure following ER was observed.For ER tablets,SLCO1B1 T521C genotype correlated with AUC 0-24 of repeat doses(P=0.010).SLCO1B1 T521C genotype had no statistically significant effect on AUC 0-24 of IR capsule of fluvastatin after single or repeated doses.In vitro study demonstrated that when the concentration of fluvastatin was low(<1μmol/l),the uptake of fluvastatin in the HEK293-OATP1B1 with SLCO1B1521TT(K m=0.18μmol/l)was faster than that with SLCO1B1521CC(K m=0.49μmol/l),On the other hand,when concentration reached to higher level(>1μmol/l),transport velocity of fluvastatin by HEK293-OATP1B1 with SLCO1B1521TT(K m=11.4μmol/l)and with SLCO1B1521TCC(K m=15.1μmol/l)tend to be the same.It suggests that the increased effect of SLCO1B1 T521C genotype on ER formulation of fluvastatin was mainly caused by lower blood concentrations.We recommend that formulation should be incorporated into future pharmacogenomics studies.
文摘The anti atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods.Fifty six rabbits were randomly divided into eight groups(n=7,each).Fluvastatin was given mixed with food at daily dose of8mg/kg starting 5 days before catheterization.Light microscope,immunohistochemistry,transmission electron microscope and RT PCR assay were applied to assess vascular smooth muscle cell (VSMC)proliferation and apoptosis, as well as oncogene expression in vascular wall. Results.At day 10 and day 15 after catheter induced denudation intima/media(I/M)thickness ratio was obviously higher, and also the percentage of PCNA positive cells and TUNEL positive cells in media was significantly higher compared with controls.The intimal hyperplasia was mostly composed of α SM actin positive cells.In rabbits given fluvastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvastatin.The overexpression of proto oncogene H ras mRNA and decreased expression of anti oncogene p53 mRNA were found after vascular injury,whereas fluvastatin significantly reduced H ras mRNA and increased p53 mRNA expression. Conclusion.Proliferation of VSMC in the media and the migration to the intima can be inhibited,and apoptosis of VSMC be induced by short term use of fluvastatin after balloon catheter denudation,independent of serum lipid change.The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.
文摘Objective To study the protective effect of fluvastatin,one of the HMG-CoA reductase inhibitors (statins),against oxygen radical-induced oxidative damages in human aortic endothelial cell,and the role of Bcl-2 in this protection.Methods Human aortic endothelial cells with or without Bcl-2 siRNA transfection were subjected to 1-100 nM of fluvastatin and 100 la hydrogen peroxide for 24 hours.Bcl-2 mRNA and protein expression were measured by Taqman quantitative PCR and Western blotting.Cell apoptosis was measured by normal and fluorescent microscopy and Cell Death Detection ELISA.Results In the Bcl-2-expressed cells,fluvastatin significantly reversed hydrogen peroxide-induced microscopic apoptosis and apoptotic DNA fragmentation,which were accompanied by a markedly upregulation of Bcl-2 expression by fluvastatin.However,the endothelial protection by fluvastatin was completely lost in Bcl-2 siRNA transfected cells.Conclusion Fluvastatin protects human endothelial cells against oxygen radical-induced cell apoptosis in vitro,and this protection seemed to be mediated in a Bcl-2 dependent pathway.(J Geriatr Cardil 12008;5:33-38)
文摘Objective: To investigate the effects of fluvastatin combined with β-receptor-blockers on cardiac function and peripheral blood NF-κB and sST2 in patients with coronary heart disease (CHD) complicated with heart failure. Methods: A total of 90 CHD patients complicated with heart failure from September 2016 to September 2017 were selected and randomly divided into the control group and the observation group, with 45 cases in each group. The control group was treated with arotinolol and the observation group was treated with arotinolol combined with fluvastatin. The clinical efficacy of the two groups after treatment was compared. The cardiac function index, blood lipid index, inflammatory factor and serum NF-κB and sST2 levels were detected and compared between the two groups. Results: The effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the cardiac function indexes of the two groups were significantly improved (P<0.05). The LVEF and LVFS of the observation group were significantly higher than those of the control group, and LVEDD and LVESD of the observation group were significantly lower those of the control group (P<0.05). The serum lipid index and inflammatory factors of the two groups were significantly decreased after treatment. The hs-CRP, TNF-α, TC and LDL-C of the observation group were significantly lower than those of the control group after treatment (P<0.05). After treatment, the serum NF-κB and sST2 were significantly decreased in both groups, and the serum NF-κB and sST2 in the observation group were significantly lower than those in the control group. There was no significant difference in the incidence of adverse reactions between the two groups (P<0.05). Conclusions: Fluvastatin combined with β-receptor-blockers can reduce the level of blood lipid and inflammatory factors more effectively and improve the clinical efficacy of the CHD patients complicated with heart failure. It can effectively reduce serum NF-κB and sST2 more effectively and improve prognosis.
基金Supported by Funds From the Yakult Bio-Science FoundationGrant-in Aid for Scientific Research from the Ministry of Education,Sports and Culture of Japan
文摘AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs)cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors on the ulceration in small intestines of rats.METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method.RESULTS: Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin)did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others(pravastatin, atorvastatin).CONCLUSION: Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.
文摘The effects of NO-Fluvastatin on proliferation of human lens epithelial cells (HLECs) and the action mechanism were investigated. Cell proliferation was assessed by MTT assay. Cell cycle was analyzed by flow cytometry. The expression of cell cycle regulatory proteins CyclinE mRNA and P21waf1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). MTT staining colorimetry showed that HLECs proliferation was markedly inhibited by NO-Fluvastatin and the effect was dependently related to time (24, 48 and 72 h) and dosage (1, 5 and 20 μmol/L). Flow cytometry revealed that NO-Fluvastatin could significantly block HLECs in the G0/G1 phase, resulting in the increased cells in the G0/G1 phase and decreased in the S phase (P<0.05). RT-PCR showed that NO-Fluvastatin could obviously inhibit the CyclinE mRNA expression and induce the P21waf1 mRNA expression as compared with the negative control groups (P<0.05). This experiment suggested that NO-Fluvastatin could suppress the proliferation of HLECs by regulating cell cycle regulatory proteins (inhibiting the expression of CyclinE mRNA and inducing the expression of P21waf1 mRNA), resulting in the arrest of HLECs in the G0/G1 phase, which can offer theory basis for NO-Fluvastatin in treating posterior capsular opacification in clinic practice.
文摘The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulation by fluvastatin were also investigated. 24 male Wistar rats were randomly divided into normal control group (n=8), diabetic nephropathy group (n=8) and fluvastatin-treated diabetic nephropathy group (15 mg/kg/d, n=8). The metabolic parameters were measured at the 8th week. The expression of transforming growth factor β 1 (TGF-β 1) and fibronectin (FN) was immunohistochemically examined. The expression of SGK1 was detected by RT-PCR and Western blot, and CTGF mRNA was assessed by RT-PCR. As compared to DN, blood glucose, 24-h urinary protein, Cer and kidney weight index were all decreased and the weight was increased obviously in group F. At the same time, mesangial cells and extracellular matrix proliferation were relieved significantly. The levels of cortex SGK1 mRNA and protein were up-regulated, and both TGF-β 1 and FN were down-regulated by fluvastatin. The mRNA of SGK1 was positively correlated with the CTGF, TGF-β 1 and FN. SGK1 expression is markedly up-regulated in the renal cortex of DN group and plays an important role in the development and progress of diabetic nephropathy by means of signal transduction. Fluvastatin suppressed the increased SGK1mRNA expression in renal cortex and postponed the development of diabetic nephropathy.
文摘OBJECTIVE The purpose of the present study was to investigate the impact of fluvas.tatin formulation on the pharmacokinetics-genetic polymorphis relationship.METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release(ER) 80 mg tablet and an immediate-release(IR) 40 mg capsule in terms of drug metabolism enzyme and transporter ge.netic polymorphisms.In this open-label,randomized,two-period,two-treatment,crossover study,ef.fects of BCRP,SLCO1B1,MDR1,CYP2C9,and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using highperformance liquid chromatography-tandem mass spectrometry.RESULTS The SLCO1 B1 T521 C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1 B1 T521 C genotype correlated with the AUC_(0-24) of repeat doses(P=0.01).The CYP2C9*3 genotype correlated with the AUC_(0-24) after the first dose IR40 mg capsule(P<0.05);however,the difference between CYP2C9*1/*1 and CYP2 C9*1/*3 was not statistically significant after repeated doses.CONCLUSION The effect of SLCO1B1T521C on fluvas.tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.
基金financial support by the National Natural Science Foundation of China (Nos. 21190033, 21372083, 21572039)National 973 Program (No. 2013CB733700)
文摘Most reported fluorescent probes have limitations in practical applications in living systems due to the strong autofluorescence background,construction of probes with near-infrared(NIR) fluorescence emission is an accessible approach for addressing this challenge.We here designed a NIR fluorescent probe for monitoring the endogenous production of H_2S in living cells.The designed probe showed significant NIR fluorescence turn-on response to H_2S with high selectivity,enabling the sensitive detection H_2S.Importantly,the probe could be applied in monitoring the endogenous production of H_2S in raw 264.7 macrophages.This study showed that fluvastatin can promote the activity of cystathionineγ-lyase(CSE) for generation H_2S.
文摘Multiple studies have investigated the associations between fluvatatin and the risk of breast cancer(BC),but their results were conflicting.A meta-analysis of observational studies published regarding this subject was conducted in the present study.It aims to estimate the associations between fluvastatin use and the risk of BC.Pubmed and chinese national knowledge infrastructure(CNKI) database was searched up to January,2015 to identify eligible observational studies,and the Newcastle-Ottawa Scale(NOS) was used to assess quality of the studies.Pooled relative risk(RR) estimates and 95% confidence intervals(CIs) were calculated(fixed effect model:Mantel-Haenszel).Heterogeneities were evaluated before the calculation.A sensitivity analysis was also conducted.In total,four studies contributed to the analysis.Overall,fluvastatin use negatively correlated with BC risk(RR = 0.74,95 % CI = 0.58,0.95).In conclusion,fluvastatin use may reduce the risk of BC,but more research is needed to confirm this finding.
