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991.
患者女,76岁,因“全身肌肉疼痛,伴乏力1周”入院。因冠心病长期服用降脂药“辛伐他汀(舒将之)20 mg/晚”,约2月前改用“辛伐他汀(京新)40 mg/晚”。入院后完善相关检查,肌酸激酶明显升高,肾功能轻度受损。诊断上考虑为:辛伐他汀导致的横纹肌溶解症。该病例特点:1)长期服用辛伐他汀未见不良反应,更换厂家及增加剂量2月后出现不良反应;2)肌酸激酶水平的显著升高;3)如此高的肌酶水平却并没有出现严重的肾功能损害,预后良好。 相似文献
992.
Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model 下载免费PDF全文
Elizabeth M. Masko Mahmoud A. Alfaqih Keith R. Solomon William T. Barry Christopher B. Newgard Michael J. Muehlbauer Nikolaos A. Valilis Tameika E. Phillips Susan H. Poulton Alexis R. Freedland Stephanie Sun Shweta K. Dambal Sergio E. Sanders Everardo Macias Michael R. Freeman Mark W. Dewhirst Salvatore V. Pizzo Stephen J. Freedland 《The Prostate》2017,77(5):446-457
993.
目的探索他汀类药物治疗激素性股骨头坏死的效果及其机制。方法根据随机数字表法将80例患者随机分为研究组和对照组。研究组患者口服辛伐他汀片,对照组患者服用活血补肾方汤剂进行治疗,12周后对上述患者进行脂联素、TNF-α、血脂、血糖检测并进行Harris和VAS评分。结果 (1)与对照组相比,研究组患者的脂联素明显升高,TNF-α、血脂和血糖明显降低(P<0.05);(2)研究组Harris评分为93.69±2.03,VAS评分为4.13±0.03,明显高于对照组(P<0.05);(3)研究组患者的总体有效率为95.0%和92.5%,显著高于对照组(80.0%和77.5%)(P<0.05);(4)随访后,研究组Harris和VAS评分差异无统计学意义(P>0.05);而对照组评分有显著变化,且差异具有统计学意义(P<0.05)。结论他汀类药物主要通过降低血脂、改善机体血流动力学等作用机制,有效干预激素性股骨头坏死的发展进程,预防患者病情的恶性进展,降低患者的发病率,值得临床推广。 相似文献
994.
Wei Yang Qiuyang Zhang Yue Yang Jiaqiu Xu Ali Fan Chung S. Yang 《Xenobiotica; the fate of foreign compounds in biological systems》2017,47(1):86-92
1.?This study aimed to investigate the potential impact of epigallocatechin-3-gallate (EGCG) on the pharmacokinetic behaviors of simvastatin and its metabolite simvastatin acid and explored the possible role of metabolizing enzymes and transporters of this food–drug interaction.2.?Female SD rats were intravenously administered with EGCG (5?mg/kg), ketoconazole (10?mg/kg) and rifampin (10?mg/kg), followed by intravenous administration of 2?mg/kg simvastatin. In vitro, the effects of EGCG on Cytochrome P450 enzymes (CYP450) and organic anion transporting polypeptides (OATPs) were studied using human hepatic microsomes and human embryonic kidney 293 (HEK293) cells overexpressing OATP1B1 or OATP1B3. The results showed that areas under concentration–time (AUC) curves of simvastatin and simvastatin acid increased by 2.21- and 1.4-fold while the clearance was reduced by 2.29- and 1.4-fold, respectively, when co-administered with EGCG. In vitro experiments suggested the inhibitory effect of EGCG on CYP enzymes (IC50: 18.37?±?1.36?μM, 26.08?±?1.51?μM for simvastatin and simvastatin acid, respectively). Simvastatin transport by OATP1B1 and OATP1B3 was also inhibited by EGCG (IC50: 8.68?±?1.27?μM and 22.67?±?1.42?μM, respectively).3.?The presently reported novel food–drug interaction between EGCG and simvastatin involves the inhibition of not only CYP450 enzymes but also OATPs by EGCG. 相似文献
995.
996.
Fabrication of β‐cyclodextrin‐mediated single bimolecular inclusion complex: characterization,molecular docking,in‐vitro release and bioavailability studies for gefitinib and simvastatin conjugate 下载免费PDF全文
997.
Simvastatin is used in treatment of hypercholesterolemia because it regulates cholesterol synthesis as a result of its β-hydroxy acid acting as an inhibitor of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA). The present communication deals with synthesis, characterization and development of accurate, precise and sensitive Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for simultaneous estimation of simvastatin and its synthetic impurities. The impurities methyl ether and β-hydroxy acid of simvastatin were synthesized in the laboratory and characterized by MS, NMR and FT-IR spectroscopy. The separation of simvastatin and its impurities was carried out on an isocratic JASCO RP-HPLC system using KYA TECH HIQ SIL C(18) column (150 × 4.6 mm internal diameter, particle size 5 μm) operating at ambient temperature using acetonitrile:water (80:20 v/v) with 0.1% orthophosphoric acid as mobile phase. The method developed for HPLC analysis of three impurities along with simvastatin was validated using ICH Q2B (R1) guidelines and it complied with these guidelines. The results of analysis were found to be in the range of 98.14% to 101.89% for all analytes with acceptable accuracy and precision. The method can be used for detection and quantification of synthetic impurities in bulk or formulations of simvastatin. 相似文献
998.
Rinaldi B Donniacuo M Esposito E Capuano A Sodano L Mazzon E Di Palma D Paterniti I Cuzzocrea S Rossi F 《British journal of pharmacology》2011,163(3):609-623
BACKGROUND AND PURPOSE
Zymosan-induced non-septic shock is a multi-factorial pathology that involves several organs including the kidneys, liver and lungs. Its complexity and diversity presents a continuing therapeutic challenge. Given their pleiotropic effect, statins could be beneficial in non-septic shock. One of the molecular mechanisms underlying the anti-inflammatory effect of statins involves the peroxisome proliferator-activated receptor (PPAR) α. We used a zymosan-induced non-septic shock experimental model to investigate the role of PPARα in the anti-inflammatory effects of simvastatin.EXPERIMENTAL APPROACH
Effects of simvastatin (5 or 10 mg·kg−1 i.p.) were analysed in PPARα knock-out (KO) and PPARα wild type (WT) mice after zymosan or vehicle administration. Organ injury in lung, liver, kidney and intestine was evaluated by immunohistology. PPARα mRNA expression and nuclear factor-κB activation were evaluated in all experimental groups, 18 h after study onset. Cytokine levels were measured in plasma, and nitrite/nitrate in plasma and peritoneal exudate. Nitric oxide synthase, nitrotyrosine and poly ADP-ribose were localized by immunohistochemical methods.KEY RESULTS
Simvastatin significantly and dose-dependently increased the zymosan-induced expression of PPARα levels in all tissues analysed. It also dose-dependently reduced systemic inflammation and the organ injury induced by zymosan in lung, liver, intestine and kidney. These effects were observed in PPARαWT mice and in PPARαKO mice.CONCLUSIONS AND IMPLICATIONS
Simvastatin protected against the molecular and cellular damage caused by systemic inflammation in our experimental model. Our results also provide new information regarding the role of PPARα in the anti-inflammatory effects of statins. 相似文献999.
The purpose of this study was to investigate the possible effects of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. HMG-CoA reductase inhibitors and diltiazem are sometimes prescribed as a combination therapy for the prevention or treatment of cardiovascular diseases. The effect of simvastatin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Simvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC(50)) of 3.0 μM. In addition, simvastatin significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. The pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after oral and intravenous administration of diltiazem to rats in the presence and absence of simvastatin (0.3 and 1.0 mg/kg). The areas under the plasma concentration-time curve (AUC) and the peak concentration (C(max)) of diltiazem were significantly (p < 0.05, 1.0 mg/kg) increased by 45.2% and 35.2%, respectively, in the presence of simvastatin compared to control. Consequently, the absolute bioavailability (AB) values of diltiazem in the presence of simvastatin (1.0 mg/kg) were significantly (p < 0.05) higher (44.8%) than that of the control group. Moreover, the relative bioavailability (RB) of diltiazem was 1.21- to 1.45-fold greater than that in the control group. The metabolite-parent AUC ratio (MR) in the presence of simvastatin (1.0 mg/kg) significantly decreased compared to the control group. This result implied that simvastatin effectively inhibited the metabolism of diltiazem. The increase in diltiazem oral bioavailability might be attributable to enhanced absorption in the small intestine via the inhibition of P-gp and to reduced first-pass metabolism of diltiazem via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver rather than renal elimination of diltiazem by simvastatin. 相似文献
1000.
Guiney WJ Beaumont C Thomas SR Robertson DC McHugh SM Koch A Richards D 《British journal of clinical pharmacology》2011,72(1):133-142