普伐他汀对鼠动脉粥样硬化及炎症因子的影响

目的 研究普伐他汀对鼠动脉粥样硬化形成过程及炎症因子的影响.方法 取40只大鼠制作动脉粥样硬化模型,随机分为正常饮食组（A）、对照组（B）、普伐他汀（C,10mg＆#183;kg-1＆#183;d-1）、普伐他汀（D,20mg＆#183;kg-1＆#183;d-1）各10只.B、C、D组定期腹腔注射维生素D破坏内皮细胞,喂养3个月,抽血检测hs-CRP,IL-6,并解剖大鼠制作病理切片,最后处死所有大鼠.结果 B组病理切片显示内膜明显增厚,管壁弥漫性隆起,内皮下含大量泡沫细胞,中膜平滑肌细胞增生.而A组内膜光滑,内皮下未见泡沫细胞,中膜平滑肌排列整齐有序,未见增生改变,C、D组内膜增生情况较B组轻,较A组重,且C组较D组增生明显.炎症因子hs-CRP,IL-6在B、C、D、A中的检测水平依次下降,B组较A组、B组较C组、B组较D组、C组较D组差异均有统计学意义（P＜0.05）.结论 普伐他汀有降低炎症因子,抑制动脉粥样硬化形成的作用.     

Effect of pravastatin on plasma sterols and oxysterols in men

Objectives The HMG-CoA reductase inhibitors, or statins, are well established in the prevention and treatment of coronary artery disease, mainly by lowering low-density lipoprotein (LDL) cholesterol levels. These compounds are structurally similar, but differ in their lipophilicity. Several studies have indicated a link between cholesterol and Alzheimer’s disease (AD), and there is also epidemiological evidence that statin treatment may decrease the prevalence of dementias. In the present study we wanted to investigate whether pravastatin treatment affects brain cholesterol metabolism. Methods A post hoc analysis was performed with plasma material from a clinical trial where 51 healthy men (35±4 years) were randomly assigned to receive either pravastatin (40 mg/day) or placebo for 6 months. Cholesterol, its precursor lathosterol, its brain-specific metabolite 24(S)-hydroxycholesterol (24S-OH-chol) and 27-hydroxycholesterol (27-OH-chol) were determined in plasma samples before and after treatment by using gas-liquid chromatography (GC)-flame ionization detection (GC-FID) and GC mass spectrometry (GC-MS). Results Besides reducing total cholesterol (−20%, P<0.001) and LDL cholesterol (LDL-C; −33%, P<0.001) concentrations, pravastatin treatment resulted in a decrease of the ratio of lathosterol to cholesterol, a surrogate marker of endogenous cholesterol synthesis, by 20% (P<0.05). Absolute concentrations of 24S-OH-chol were not altered, but its ratio to cholesterol slightly increased by 15% (P<0.05). 27-OH-chol concentrations as well as its ratio to cholesterol were both significantly altered due to pravastatin treatment (−7% and +14%, P<0.05 for both, respectively). Conclusions The treatment with pravastatin 40 mg once a day for 6 months does not affect brain cholesterol metabolism as judged by plasma concentrations of 24(S)-hydroxycholesterol.     

Effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolaemia: a comparison of morning and evening administration

In order to determine whether there is a difference in the effect of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on cholesterol synthesis between the morning and the evening, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1, eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening after a 1-week wash-out period. In study 2, five subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash-out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respectively. Urinary mevalonate excretion was significantly reduced at 4–8 h after pravastatin administration in the morning (51 vs 19 nmol · h^–1) and at 4–16 h after pravastatin administration in the evening (56 vs 27 nmol · h^–1). Daily urinary mevalonate excretion was equally and significantly reduced by pravastatin in the morning or evening. In conclusion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentrations.     

氟康唑滴眼液治疗外耳道真菌病的疗效

目的观察氟康唑滴眼液治疗外耳道真菌病的临床疗效。方法将343例(476耳)外耳道真菌病患者随机分为治疗组与对照组,治疗组211例(298耳)使用氟康唑滴眼液治疗,对照组132例(178耳)使用水杨酸酒精滴耳液治疗,应用疗效评定标准评定疗效。结果治疗组、对照组的总有效率分别为95.6%、61.2%(P<0.05)。结论采用氟康唑滴眼液治疗外耳道真菌病疗效显著。     

辛伐他汀与氟伐他汀的调脂疗效观察

目的:比较辛伐他汀与氟伐他汀的调脂疗效.方法:将66例高脂血症患者随机分为辛伐他汀组(33例)和氟伐他汀组(33例).治疗4周和8周后比较各组的疗效.结果:辛伐他汀组和氟伐他汀组两组疗效比较差异无显著性(P>0.05).结论:辛伐他汀与氟伐他汀疗效相同,并且能够取得满意的疗效.     

Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam

Objective: Midazolam is a short-acting benzodiazepine hypnotic extensively metabolized by CYP3A4 enzyme. Orally ingested azole antimycotics, including fluconazole, interfere with the metabolism of oral midazolam during its absorption and elimination phases. We compared the effect of oral and intravenous fluconazole on the pharmacokinetics and pharmacodynamics of orally ingested midazolam. Methods: A double-dummy, randomized, cross-over study in three phases was performed in 9 healthy volunteers. The subjects were given orally fluconazole 400 mg and intravenously saline within 60 min; orally placebo and intravenously fluconazole 400 mg; and orally placebo and intravenously saline. An oral dose of 7.5 mg midazolam was ingested 60 min after oral intake of fluconazole/placebo, i.e. at the end of the corresponding infusion. Plasma concentrations of midazolam, α-hydroxymidazolam and fluconazole were determined and pharmacodynamic effects were measured up to 17 h. Results: Both oral and intravenous fluconazole significantly increased the area under the midazolam plasma concentration-time curve (AUC_0–3, AUC_0–17) 2- to 3-fold, the elimination half-life of midazolam 2.5-fold and its peak concentration (C_max) 2- to 2.5-fold compared with placebo. The AUC_0–3 and the C_max of midazolam were significantly higher after oral than after intravenous administration of fluconazole. Both oral and intravenous fluconazole increased the pharmacodynamic effects of midazolam but no differences were detected between the fluconazole phases. Conclusion: We conclude that the metabolism of orally␣administered midazolam was more strongly inhibited by oral than by intravenous administration of fluconazole. Received: 1 July 1996 / Accepted in revised form: 4 September 1996     

氟伐他汀对扩张型心肌病心室重构和血浆脑钠肽水平的影响

目的：探讨氟伐他汀对扩张型心肌病（ DCM ）心室重构和血浆脑钠肽（ BNP ）水平的影响。方法选择64例DCM患者,采用随机数字表法分为干预组与对照组各32例。两组均采用常规药物治疗,包括血管紧张素转换酶抑制剂、β受体阻滞剂、利尿剂等。干预组在常规药物治疗基础上加用氟伐他汀40 mg／d。两组均于干预前及干预6个月后分别检查血浆BNP水平及心室重构各项指标,采用Pearson单因素相关分析比较各指标的相关性。结果干预组总有效率明显优于对照组（87．51％与65．63％,χ^2＝4．730,P＜0．05）;两组干预6个月后,血浆BNP水平明显下降,左室射血分数（ LVEF）、左室收缩末内径（ LVESD）、左室舒张末内径（ LVEDD）及相对室壁厚度（ RWT）均明显改善。 BNP水平与LVEF和RWT均呈负相关（ r＝－0．45、－0．39,均P＜0．05）,与LVESD和LVEDD均呈正相关（r＝0．35、0．44,均P＜0．05）。结论氟伐他汀能明显降低DCM血浆BNP水平,改善心室重构。     

阿托伐他汀与氟伐他汀治疗高胆固醇血症的对比研究

目的　探讨阿托伐他汀 (立普妥 )与氟伐他汀 (来适可 )对高胆固醇血症病人疗效及安全性。方法　 10 0例高胆固醇血症随机分成阿托伐他汀组 5 0例和氟伐他汀组 5 0例 ,治疗 6周后观察比较。结果　阿托伐他汀及氟伐他汀均能明显降低TC、TG、LDL C水平 (P <0 0 1或P <0 0 5 ) ,阿托伐他汀降TC、TG、LDL C的作用强于氟伐他汀 (P <0 0 5 ) ,两药均能升高HDL C水平 (P <0 0 5 ) ,但两组比较未达到显著差异 (P >0 0 5 )。两药不良反应均比较小 ,耐受性好。结论　阿托伐他汀降TC、TG、LDL C的作用优于氟伐他汀 ,但升高HDL C水平相似 ,两药均有良好的安全性。     

The pharmacokinetics of pravastatin in patients on chronic hemodialysis

Objective: The single-dose and steady-state pharmacokinetics of the HMG CoA reductase inhibitor pravastatin and its two metabolites, SQ 31 906 and SQ 31 945, were evaluated in 12 hemodialysis patients. A single 20-mg i.v. dose was employed, followed by daily oral dosing of 20 mg over four hemodialysis intervals. Results: No statistical differences in the pharmacokinetics of pravastatin or SQ 31 906 were evident when comparing the first and last days of oral dosing with pravastatin. The pharmacokinetic parameters of pravastatin and SQ 31 906 were similar to those of healthy volunteers. SQ 31 945, the inactive polar metabolite, did accumulate in dialysis patients, as evidenced by an accumulation index of 1.7 ± 1.0. Although metabolic clearance is the predominant mode of elimination of pravastatin, hemodialysis clearances of pravastatin, SQ 31 906 and SQ 31 945 will contribute to total body clearance since dialytic clearance ranged from 40 to 80 ml · min⁻¹. Conclusion: Pravastatin can be safely administered in the usual dosages to subjects with renal failure on hemodialysis and no change in dosing is necessary. Received: 7 January 1997 / Accepted in revised form: 12 May 1997     

氟伐他汀对肺动脉高压大鼠5-羟色胺转载体表达的影响

目的观察氟伐他汀对野百合碱(MCT)所致的肺动脉高压大鼠肺组织5-羟色胺转载体(5-HTT)表达的影响。方法62只大鼠随机分为3组:①M+F组:大鼠首先给予MCT(40 mg/kg)皮下注射和氟伐他汀(1 mg/kg)灌胃,每日各1次,连续2周。第3~6周继续按氟伐他汀初始给药方案灌胃,不再进行MCT皮下注射。②MCT组:实验前2周给予MCT(40 mg/kg)1次/d皮下注射,第3~6周末给予同氟伐他汀等体积的0.9%盐水灌胃;③Saline组:分别于实验前2周及第3~6周给予等体积的盐水皮下注射和灌胃。分别于不同时间点,对大鼠的血流动力学及相关参数和5-HTT的表达情况进行测定。结果MCT组大鼠于实验第2周末即出现显著的肺动脉高压伴5-HTT蛋白水平异常增高,且在观察期间逐渐增高。M+F组大鼠第6周末出现肺动脉压异常增高,但未伴5-HTT表达增高。结论氟伐他汀能有效抑制5-HTT表达上调,该作用可能与其对大鼠肺动脉高压的抑制作用有关。     

沥水调脂胶囊与氟伐他汀治疗原发性高脂血症的疗效比较

目的　以氟伐他汀为参照研究沥水调脂胶囊的调脂和抗动脉粥样硬化的疗效和安全性。方法　将 6 0例高脂血症病人随机单盲分为两组 ,分别投以沥水调脂胶囊和氟伐他汀 ,疗程 8周 ,观察调脂疗效、不良反应及对血浆一氧化氮 (NO)、氧化型低密度脂蛋白胆固醇 (oxLDL)水平的影响。结果　两组经治疗后TC、TG、LDL C、oxLDL、TC HDL C/HDL C显著性降低 ,HDL C均无显著性升高 ,血浆NO水平均有显著性升高 ,两组药物的不良反应均较轻微。以上各指标在治疗前后两组间比较差异均无显著意义。结论　沥水调脂胶囊的降脂疗效较确切 ,且不良反应少 ,值得临床推广应用。     

HPLC法分析普伐他汀

采用高效液相色谱法分析发酵液中普伐他汀和compactm的含量.色谱柱为Spherisorb C18(10μm)4.6mm×240mm,流动相为甲醇一0.2mol/L乙酸铵水溶液(体积比5347).方法简便、快速、有效,在科研和生产上具有很强的实用性.     

Increase or decrease of HDL-cholesterol concentrations during pravastatin treatment depending on the pre-treatment HDL cholesterol levels

Objective: The effect of pravastatin was evaluated using patient data accumulated in the data base of a hospital information system (HIS). Methods: We selected 130 patients treated with pravastatin 10 mg per day, for a minimum period of 4 weeks. Results: In the t test analysis, the reduction rates of total cholesterol (TC) and low-density lipoprotein (LDL) levels for pravastatin administration were 18%, and 27%, respectively. These values were similar to previous reports. The high-density lipoprotein (HDL) level, however, did not change significantly, although previous reports have shown an elevation of HDL levels. In an attempt to explain the origin of this difference, we studied the pretreatment value dependence of the cholesterol change using regression analysis. We found that pravastatin raised the HDL level in those cases where pretreatment values were lower than 58 mg · dl⁻¹ and reduced it for higher values. We also showed that the reductions of TC, LDL and triglyceride (TG) levels correlated positively with their pretreatment values. Received: 22 August 1995 / Accepted in revised form: 31 January 1997     

氟伐他汀对尼古丁诱导血管内皮功能障碍的保护作用

目的观察尼古丁对人脐静脉内皮细胞白介素(IL)-8表达的影响,及氟伐他汀对尼古丁诱导人脐静脉内皮细胞表达的干预作用,以及这一过程中核转录因子(NF)-κB的调节机制。方法采用人脐静脉内皮细胞株传代培养,细胞随机分为4组,空白对照组:无血清DMEM培养基代替干预因素;尼古丁组:在无血清培养基中加入100 nmol/L尼古丁孵育内皮细胞24 h;氟伐他汀组:在培养基中10-5mol/L氟伐他汀孵育内皮细胞1 h后,100 nmol/L尼古丁孵育内皮细胞24 h;NF-κB抑制剂组:100μmol/L PDTC和100 nmol/L尼古丁孵育内皮细胞24 h,收集细胞标本及培养液。ELISA法检测内皮细胞培养液中IL-8的蛋白表达水平,Trans AM(tm)NF-κBp50检测试剂盒检测细胞NF-κB的活性。结果尼古丁组NF-κB活性较空白对照组明显升高(P<0.05);氟伐他汀组NF-κB活性较尼古丁组显著下降(P<0.05)。NF-κB抑制剂组较尼古丁组IL-8的蛋白表达明显下降(P<0.05),氟伐他汀组较尼古丁组IL-8的蛋白表达明显下降(P<0.05)。结论尼古丁可通过激活人脐静脉内皮细胞NF-κB的活性,从而诱导IL-8的表达;氟伐他汀可拮抗尼古丁诱发的NF-κB的活化,抑制尼古丁诱导的IL-8的表达,还可拮抗尼古丁引起的内皮功能紊乱,改善内皮细胞功能。     

Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes

Fluconazole-entrapped multilamellar liposomes were prepared using the thin-film hydration method. The effects of cholesterol molar ratio, charge-inducing agents, and α-tocopherol acetate on encapsulation efficiency values and in vitro drug release of multilamellar liposomes were studied. Freeze-dried liposomal products were prepared with or without cryoprotectants. Results showed that incorporation of stearylamine resulted in an increased entrapment of fluconazole, whereas incorporation of dicetyl phosphate decreased the drug entrapment efficiency. The incorporation of α-tocopherol acetate into fluconazole multilamellar liposomes resulted in the increase of entrapment efficiency of fluconazole liposomes. In vitro release studies revealed that incorporation of cholesterol into multilamellar liposomal formulations decreased drug permeability from formulations. Positively charged fluconazole multilamellar liposomes gave rise to a slow release rate compared to neutral liposomes whereas negatively charged fluconazole liposomes showed a rapid release rate. Physical stability studies showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute compared to fluffy easily reconstituted cakes upon using cryoprotectants. Fluconazole retained in freeze-dried liposomes without cryoprotectants was 63.452% compared to 91.877% using three grams of trehalose as a cryoprotectant per gram lipid in positively charged multilamellar liposomes. Physical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison with those of a solution product.     

氟伐他汀对老年高血压肾病患者肾功能及炎性因子的影响

目的探讨氟伐他汀对高血压肾病老年患者肾功能及炎性因子的影响。方法将轻中度老年高血压肾病患者30例随机分为治疗组和对照组各15例。治疗组在常规口服降压药物的基础上加用氟伐他汀40mg/d,共4周;对照组仅口服常规降压药物。检测治疗前及治疗4周后患者血清肌酐(Scr)、尿素氮(BUN)及C-反应蛋白(CRP)水平。结果治疗组治疗后BUN、Scr及CRP水平均显著降低,且低于对照组,差异均有统计学意义(P<0.05)。结论氟伐他汀可显著改善高血压肾病老年患者的肾功能,降低炎性因子的影响。     

普伐他汀对急性冠状动脉综合征患者血浆可溶性CD40配体水平影响的研究

目的观察普伐他汀对急性冠状动脉综合征(ACS)患者血浆可溶性CD40配体(sCD40L)水平的影响。方法选择ACS患者38例,稳定性心绞痛(SAP)患者32例,正常健康体检者40例,采用酶联免疫吸附法(ELISA)测定其血浆可溶性sCD40L浓度,并在入院后立即给予ACS患者及SAP患者服用普伐他汀(20mg/d),8周后复查其血浆可溶性sCD40L。结果ACS患者血浆sCD40L水平高于SAP组及对照组,SAP组与对照组之间无差别;血浆sCD40L水平与血TC、LDL-C呈正相关,与HDL-C呈负相关;普伐他汀治疗8周后ACS患者血浆sCD40L水平下降,而SAP组血浆sCD40L水平无明显改变。结论ACS患者血浆sCD40L水平升高,可能与其发病机制密切相关,血浆sCD40L水平可作为ACS诊断及病情判断的重要指标;普伐他汀能降低ACS患者血浆sCD40L水平,对于ACS的临床治疗有着重要的意义。     

特比萘酚联合氟康唑治疗真菌性角膜炎的效果分析

目的研究特比萘酚联合氟康唑治疗真菌性角膜炎的效果。方法选取本院2009年6月～2011年2月收治的52例真菌性角膜炎患者,随机分为对照组与治疗组,每组各26例。对照组使用氟康唑进行治疗,治疗组使用氟康唑联合特比萘酚进行治疗。结果治疗组的有效率为92．3％,明显高丁对照组的80．8％,治疗组的治愈天数为（36．19±13．18）d明显短于治疗组的（23．75±12．92）d;两组的不良反应比较,后异有统计学意义（P〈0.01）。结论特比萘酚联合氟康唑治疗真菌性角膜炎的治疗效果较好,值得临床推广应用。     

普伐他汀对Ⅱ型糖尿病伴高脂血症的疗效及对胰岛素敏感性指数的影响

目的 研究普伐他汀对Ⅱ型糖尿病伴高脂血患者的疗效及对胰岛素敏感性指数的影响。方法 对Ⅱ型糖尿病伴高脂血症的患者38例采用自身单盲试验,口服普伐他汀者分别于治疗前及治疗后1个月及3个月观察空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素敏感性指数(ISI=1/FBG×FINS)及TC、HDL-C、LDL-C、TG、TC/HDL-C的变化。结果 普伐他汀治疗3个月后,TC、LDL-C、TG及TC/HDL-C分别为33.4％、33.2％、44.3％,较治疗前明显下降(P<0.01),HDL-C上升14.6％,但升高不显著(P>0.05),FBG及FINS则同治疗前相差不明显,ISI较治疗前明显升高(P<0.05)。结论 本研究发现普伐他汀具有明显降低Ⅱ型糖尿病患者高TC、LDL-C、TG的作用,但对升高HDL-C不明显,并有降低体重指数(BMI),提高ISI作用,其提高ISI的作用与血脂下降有关。     

普伐他汀对慢性心力衰竭患者心功能及血清C反应蛋白的影响

目的 探讨普伐他汀对慢性心力衰竭(CHF)患者心功能及血清C反应蛋白(CRP)水平的影响.方法 90例CHF患者随机分为他汀组(45例)和对照组(45例).他汀组在常规治疗基础上加用普伐他汀40mg/d;对照组常规治疗.两组患者治疗前、治疗后3个月检测血清CRP及行超声心动图检查测定左心室射血分数(LVEF).结果 两组患者治疗3个月后与治疗前比较,TC、血清CRP水平均有不同程度降低,且他汀组血清CRP水平较对照组明显下降[(15.47±9.83)mg/L,(20.31±7.15)mg/L,P<0.05],LVEF较对照组明显上升[(45.70±7.01)%,(38.34±5.31)%,P<0.05];血清CRP水平与LVEF呈负相关(r=-0.495,P<0.05).结论 普伐他汀能改善CHF患者的预后;血清CRP水平可作为治疗CHF的一个灵敏观察指标.