唑来磷酸联合普伐他汀治疗绝经后妇女骨质疏松

目的探讨唑来磷酸和普伐他汀对绝经后妇女骨质疏松的治疗作用。方法前瞻性研究我院92例绝经后骨质疏松女性患者,随机分成唑来磷酸＋普伐他汀组（A组）、唑来磷酸组（B组）和普伐他汀组（C组）,分别按照各自的方案治疗并检测各组治疗前后骨密度值、骨钙素含量。结果各组患者治疗前后骨密度值、骨钙素含量的差异有统计学意义（P〈0.05）,A组患者治疗后骨密度值、骨钙素含量均较B、C组高,差异有统计学意义（P〈0.05）,但B、C两组患者治疗后骨密度值、骨钙素含量差异无统计学意义（P〉0.05）。结论联合使用唑来磷酸和普伐他汀对骨质疏松有更好的治疗作用。     

唑来磷酸联合利拉鲁肽治疗2型糖尿病合并骨质疏松的临床价值分析

目的 探讨唑来磷酸联合利拉鲁肽治疗2型糖尿病合并骨质疏松的临床价值.方法 92例2型糖尿病合并骨质疏松的患者,随机分为观察组与对照组,各46例.对照组给予唑来磷酸治疗,观察组给予唑来磷酸联合利拉鲁肽治疗,两组均持续治疗3个月.比较两组治疗前后糖代谢指标、骨代谢指标、骨密度(BMD)、预后情况、不良反应发生情况.结果 治...     

经皮椎体后凸成形术联合唑来磷酸治疗骨质疏松椎体压缩性骨折的临床研究

目的 观察骨质疏松椎体压缩性骨折采用经皮椎体后凸成形术联合唑来磷酸治疗的效果.方法 选择本院2013年8月~2015年8月收治的骨质疏松椎体压缩性骨折患者37例,回顾性分析其临床资料,观察治疗效果.结果 37例患者手术时间(44.1±2.6)min;骨水泥注入量(4.1±0.9)mL.术后12个月时,疼痛评分、Beck值低于术后1周,Cobb角高于术后1周,差异具有统计学意义(P<0.05).结论 应用经皮椎体后凸成形术联合唑来磷酸治疗骨质疏松椎体压缩性骨折患者时,具有良好的治疗效果,可提升患者的生活质量.     

唑来磷酸联合运动训练对去势后大鼠骨质密度及血清生化指标的影响

目的探讨应用唑来磷酸治疗联合运动训练对于预防绝经后骨质疏松的生物学作用。方法选取雌性SD大鼠45只,随机分为正常对照组、单纯去势组以及治疗组3组,正常对照组行假手术,剩余2组行卵巢切除术。正常对照组、单纯去势组自由活动,治疗组术后每日行跑步训练,同时给予唑来磷酸治疗,给予皮下注射唑来磷酸0.5 mg/kg·d。术后12周分别做所有动物的骨组织病理学检测,测量腰椎骨密度以及血清中钙磷离子、碱性磷酸酶和骨钙素水平。结果腰椎骨密度测定显示正常对照组及治疗组明显高于单纯去势组;血清生化指标检测显示正常对照组及治疗组钙离子、碱性磷酸酶和骨钙素水平均明显低于单纯去势组;腰椎椎体组织病理学检测显示治疗组骨小梁质量优于单纯去势组。结论唑来磷酸联合运动训练对于预防和治疗绝经后骨质疏松有着很好的效果。     

唑来膦酸联合来曲唑治疗绝经后乳腺癌骨转移42例疗效观察

目的:对比唑来膦酸或唑来膦酸联合来曲唑治疗绝经后乳腺癌骨转移的临床效果.方法:选取我院肿瘤内科收治的84例绝经后乳腺癌骨转移患者,随机分成两组,每组42例.唑来膦酸组给予唑来膦酸,联合组给予唑来膦酸和来曲唑.对比两组临床疗效、止痛效果和不良反应发生情况.结果:治疗3个月后,联合组治疗总有效率为42.9％,止痛总有效率为78.6％,明显高于唑来膦酸组的19.0％和57.1％(P<0.05).两组不良反应事件发生率无明显差异(P>0.05).结论:唑来膦酸和来曲唑联合治疗绝经后乳腺癌骨转移,能够取得比较理想的治疗效果,有效缓解疼痛,不良反应较轻.     

椎体成形术联合唑来磷酸治疗椎体转移癌27例

摘要 目的探讨经皮椎体成形术（PVP）联合唑来磷酸治疗椎体转移癌的临床应用价值。方法椎体转移癌患者56例,分为PVP治疗组29例,接受PVP术联合治疗组27例,接受PVP术,联合唑来磷酸4 mg加0.9%氯化钠溶液100 mL静脉滴注,每3～4周1次。手术后疼痛缓解程度应用视觉模拟评分法评估,采用日常生活自理能力（ADL）量表对治疗后患者生活质量进行评估,观察患者6个月后疼痛复发情况。结果两组患者1个月后疼痛均明显缓解（P＞0.05）。手术后6个月,PVP治疗组骨转移疼痛复发率为34.48%,联合治疗组复发率为11.1%（P＜0.05）。手术后1年,PVP治疗组患者ADL总分为（79.3±10.9）分,联合治疗组（89.6±10.2）分,两组患者手术后ADL总分差异有统计学意义（P＜0.05）。结论PVP联合唑来磷酸治疗椎体转移癌临床镇痛疗效明显,能够加强脊柱稳定性,有效预防椎体病理性骨折并发症发生,改善患者生活质量。     

唑来膦酸联合VD治疗老年骨质疏松的疗效及安全性评价

目的:观察唑来膦酸联维生素D(VD)治疗老年骨质疏松的疗效及安全性。方法:选取2016年1月～2017年3月医院收治的老年骨质疏松患者72例为研究对象,随机数表法均分为对照组和观察组,每组36例。对照组给予VD治疗,观察组在对照组基础上给予唑来膦酸治疗,比较两组治疗有效率、不良反应发生率。结果:观察组治疗有效率91.67%高于对照组72.22%(P0.05);观察组不良反应发生率19.44%与对照组25.00%差异无统计学意义(P0.05)。结论:唑来膦酸联合VD能提高老年骨质疏松的治疗有效率,不良反应发生率低。     

唑来磷酸联合化疗治疗非小细胞肺癌骨转移的疗效观察

目的评价唑来磷酸联合化疗治疗非小细胞肺癌骨转移的疗效及不良反应。方法将48例非小细胞癌骨转移患者随机分为治疗组和对照组,每组24例,治疗组给予唑来磷酸同步化疗治疗,对照组单用唑来磷酸。结果治疗组和对照组的止痛总有效率分别为79.2%、54.2%,治疗组效果明显优于对照组,差异有统计学意义（P〈0.05）。结论唑来磷酸联合化疗治疗非小细胞肺癌骨转移有较好疗效,值得临床推广应用。     

唑来磷酸治疗恶性肿瘤骨转移性疼痛的临床研究

目的评价唑来磷酸缓解恶性肿瘤骨转移性疼痛的效果。方法40例恶性肿瘤骨转移性疼痛患者,给予唑来磷酸注射液4 mg,生理盐水稀释后静脉滴注,每4周1次,至少连续3次。结果40例患者临床骨转移止痛总有效率为70%;活动能力改善总有效率为72.5%;生活质量改善总有效率为67.5%。结论唑来磷酸注射液可有效缓解恶性肿瘤骨转移疼痛,显著改善患者的生活质量。     

Liver-specific distribution of rosuvastatin in rats: comparison with pravastatin and simvastatin.

Rosuvastatin is a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. The liver is the target organ for the lipid-regulating effect of rosuvastatin; therefore liver-selective uptake of this drug is a desirable property. The aim of this study was to investigate, and compare with pravastatin and simvastatin, the tissue-specific distribution of rosuvastatin. Bolus intravenous doses (5 mg/kg) of radiolabeled rosuvastatin, pravastatin, and simvastatin were administered to rats, and initial uptake clearance (CL(uptake)) in various tissues was calculated. Hepatic CL(uptake) of rosuvastatin (0.885 ml/min/g tissue) was significantly (p < 0.001) larger than that of pravastatin (0.703 ml/min/g tissue), and rosuvastatin was taken up by the hepatic cells more selectively and efficiently than pravastatin. Hepatic CL(uptake) of simvastatin (1.24 ml/min/g tissue) was significantly larger than that of rosuvastatin (p < 0.01) and pravastatin (p < 0.001). However, adrenal CL(uptake) of simvastatin (1.55 ml/min/g tissue) was larger than hepatic CL(uptake), and simvastatin was distributed to other tissues more easily than rosuvastatin. Microautoradiography of the liver, spleen, and adrenal was undertaken 5 min after administration of the study drugs; distribution was quantified by counting the number of silver grains. After administration of rosuvastatin and pravastatin, silver grains were distributed selectively in the intracellular space of the liver, but more rosuvastatin (3.3 +/- 1.0 x 10(5) particles/mm(2)) than pravastatin (2.0 +/- 0.3 x 10(5) particles/mm(2)) tended to distribute to the liver. Simvastatin was less liver-specific (it also distributed to the spleen and adrenal). The results of this study indicated that rosuvastatin was taken up by hepatic cells more selectively and more efficiently than pravastatin and simvastatin.     

Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats

Background and purpose:

This study investigates the effect of pravastatin on blood pressure, cardiovascular remodelling and impaired endothelial function induced as early signs of cardiovascular disease in young spontaneously hypertensive rats (SHR).

Experimental approach:

Eight-week-old SHR were treated for 4 weeks with pravastatin (20 mg·kg⁻¹·day⁻¹). Systolic blood pressure was measured periodically during the study using the tail-cuff method. At the end of the study, the left ventricular weight /body weight ratio was used as an index of left ventricular hypertrophy (LVH). Vascular function, superoxide (O₂^−.) production and structure were studied in aortic rings. Lipid peroxidation was measured in plasma (thiobarbituric acid reactive substances assay).

Key results:

Systolic blood pressure was lower in treated SHR than in control SHR, at the end of the study (171 ± 1 vs. 159 ± 2 mmHg, P < 0.05), and LVH was significantly reduced by pravastatin (2.7 ± 0.02 vs. 2.5 ± 0.01 mg·g⁻¹, P < 0.05). Vascular responses to sodium nitroprusside and phenylephrine were similar in both groups; nevertheless, the relaxation response to acetylcholine was higher in the treated rats (45.6 ± 2.6 vs. 58.1 ± 3.2 %, P < 0.05). Vascular O₂^−. and plasma thiobarbituric acid reactive substances were reduced by pravastatin treatment, and urinary nitrites was elevated. Finally aortic wall became thinner after pravastatin treatment.

Conclusions and implications:

Chronic treatment with pravastatin attenuated the increase of systolic blood pressure in SHR, prevented early LVH and improved vascular structure and function. These effects were accompanied by decreased measures of oxidative stress and improvements in NO production.     

Disposition and metabolism of pravastatin sodium in rats, dogs and monkeys.

Pravastatin sodium (pravastatin) is a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and was found to be highly effective in animals and humans, in lowering the plasma cholesterol level by inhibiting cholesterol synthesis selectively in the liver. In the present study the disposition and metabolism of pravastatin was studied in rats, dogs and monkeys using [14C]-labelled compound. The extent of absorption was approximately 70% in rats and 50% in dogs. Tissue distribution examined by both whole-body autoradiography and radioactivity measurement demonstrated that the drug was selectively taken up by the liver, a target organ of the drug, and excreted via bile mainly in unchanged form. Since pravastatin excreted by the bile was reabsorbed, the enterohepatic circulation maintained the presence of unchanged pravastatin in the target organ. The profiles of metabolites were studied in various tissues and excreta and a metabolic pathway of pravastatin was proposed.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Biliary excretion of pravastatin and taurocholate in rats with bile salt export pump (Bsep) impairment

The bile salt export pump (BSEP) is expressed on the canalicular membrane of hepatocytes regulating liver bile salt excretion, and impairment of BSEP function may lead to cholestasis in humans. This study explored drug biliary excretion, as well as serum chemistry, individual bile acid concentrations and liver transporter expressions, in the SAGE Bsep knockout (KO) rat model. It was observed that the Bsep protein in KO rats was decreased to 15% of that in the wild type (WT), as quantified using LC–MS/MS. While the levels of Ntcp and Mrp2 were not significantly altered, Mrp3 expression increased and Oatp1a1 decreased in KO animals. Compared with the WT rats, the KO rats had similar serum chemistry and showed normal liver transaminases. Although the total plasma bile salts and bile flow were not significantly changed in Bsep KO rats, individual bile acids in plasma and liver demonstrated variable changes, indicating the impact of Bsep KO. Following an intravenous dose of deuterium labeled taurocholic acid (D4‐TCA, 2 mg/kg), the D4‐TCA plasma exposure was higher and bile excretion was delayed by approximately 0.5 h in the KO rats. No differences were observed for the pravastatin plasma concentration–time profile or the biliary excretion after intravenous administration (1 mg/kg). Collectively, the results revealed that these rats have significantly lower Bsep expression, therefore affecting the biliary excretion of endogenous bile acids and Bsep substrates. However, these rats are able to maintain a relatively normal liver function through the remaining Bsep protein and via the regulation of other transporters. Copyright © 2016 John Wiley & Sons, Ltd.     

普伐他汀对糖尿病大鼠动脉组织基因谱表达的影响

目的:应用基因芯片探讨普伐他汀对糖尿病大鼠动脉组织基因谱差异性表达的影响。方法:33只SD雄性大鼠随机分为正常对照组、糖尿病组(腹腔单次注射链脲佐菌素60 mg·kg~(-1)诱导糖尿病)和糖尿病普伐他汀治疗组(普伐他汀50 mg·kg~(-1)·d~(-1),共4 wk),取其主动脉,用cy3和cy5两种荧光染料通过逆转录反应将动脉的mRNA分别标记成2种探针,并与载有一组靶基因的基因芯片进行杂交,通过计算机扫描分析得出差异表达的某些基因。结果:糖尿病组筛选出相关表达差异的基因109条,糖尿病普伐他汀治疗组75条。糖尿病组中有37条表达增高的基因(与脂肪酸、葡萄糖、胆固醇、能量代谢以及炎症免疫反应有关)在普伐他汀治疗后表达明显降低。结论:普伐他汀能够改变糖尿病动脉组织多种基因的差异性表达,从而在多环节上有抗糖尿病血管病变的作用。     

Differential effects of pravastatin on the pharmacokinetics of paroxetine in normal and diabetic rats

1.?Diabetes is often accompanied with depression and hypercholesterolemia. It is possible that paroxetine and pravastatin are co-administered to diabetic patients. The aim of this study was to research the differential effect of pravastatin on plasma exposure of paroxetine in normal and diabetic rats.

2.?Pharmacokinetics of paroxetine was investigated following oral administration of paroxetine with and without pravastatin in normal and diabetic rats. Effects of pravastatin on metabolism, intestinal absorption and hepatic uptake of paroxetine were investigated. Activity and expression of hepatic Oatp1 and Oatp2 were also assessed.

3.?Pravastatin decreased plasma exposure of paroxetine in normal rats, but increased exposure of paroxetine in diabetic rats. Pravastatin neither affected metabolism nor intestinal absorption of paroxetine. Data from hepatocytes demonstrated that hepatic uptake of paroxetine were involved in Oatp1 and Oatp2. Diabetes suppressed Oatp1 activity and expression, but enhanced Oatp2 activity and expression. Pravastatin stimulated Oatp1 but inhibited Oatp2 activity.

4.?We concluded that differential effects of pravastatin on plasma exposure of paroxetine in normal and diabetic rats was partly due to the fact that diabetes suppressed Oatp1 activity and expression but enhanced Oatp2 activity and expression as well as that pravastatin stimulated Oatp1 activity but inhibited Oatp2 activity.     

Combined therapy with probucol and pravastatin in hypercholesterolaemia

Summary The effect of co-administration of low doses of pravastatin to hypercholesterolaemic patients already receiving long-term probucol treatment (mean 500–1,000 mg/day for 350 days) were investigated. Pravastatin 5 mg/day (Group 1; 12m, 13f; mean age 59.1 y) or 10 mg/day (Group 2; 8m, 11f; mean age 60.8 y) was administered, and blood was taken after 0, 3, 6, and 12 months. Both groups showed a significant reduction in serum total cholesterol (TC), phospholipid (PL), low density lipoprotein-cholesterol (LDL-C), LDL-triglyceride (TG), LDL-PL, apolipoprotein (apo) B, and apo E after the combined therapy. These levels were reduced more in Group 2 than in Group 1 subjects. In Group 2, significant falls in serum TG and apo CII were also observed. The changes in TC, PL, LDL-C, apo B, apo CII and apo E were dependent upon the dose of pravastatin, as assessed by two-way analysis of variance. Serum high density lipoprotein (HDL)₃-C, apo AI and apo AII were slightly but significantly increased in both groups after 12 months of combined therapy, but the increase was not sufficient to reverse the probucol-induced lowering of the HDL level. We conclude that combined therapy resulted in a significant reduction in atherogenic lipoproteins and apolipoproteins, and an increasing dose of pravastatin (5 mg to 10 mg daily) made the lipid lowering effect more prominent. The reduction in serum HDL-C due to long-term probucol administration was not reversed by the addition of pravastatin. Part of this work was presented at the 9th International Symposium on Atherosclerosis, Chicago, 7th October, 1991