Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers

Objective: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release (ER) felodipine and controlled-release (CR/ZOK) metoprolol␣compared with the free combination of felodipine ER metoprolol CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine and metoprolol when administered as ER formulation. Methods: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis in six subjects. Results: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%) except for a minor deviation regarding C_max of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding pharmacodynamics was detected between the fixed combination and the corresponding free combination. Conclusion: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered as the fixed combination. Received: 29 October 1996 / Accepted in revised form: 21 March 1997     

非洛地平缓释片在兔体内药物动力学和生物利用度比较

目的 比较几种国产非洛地平缓释片在兔体内的药物动力学和生物利用度.方法 用高效液相色谱法测定兔口服药物后血浆中的药物浓度,以普通非洛地平片作为参照,计算其药物动力学和生物利用度.结果 在1.0-80μg·L-1范围内,非洛地平血浆药物浓度与色谱峰高呈良好的线性关系.单剂量兔血浆中非洛地平缓释片动力学参数不同产品存在差异,相对于普通制剂的生物利用度分别为179%、162%、122%.结论 不同产品非洛地平缓释片药物动力学和生物利用度存在差别.     

心达康对老年高血压病人血清一氧化氮的影响

目的：观察老年高血压一氧化氮（NO）的水平变化及心达康对其的影响。方法：应用比色法测定52例老年高血压病人和30例正常人的血清（NO）水平,其中20例在应用心达康,26例用非洛地平治疗2－4周后,复查血清（NO）水平。结果：老年高血压病人血清（NO）水平较对照组明显降低（P＜0．01）,Ⅱ-Ⅲ级病人明显低于I级病人（P＜0．01）,经心达康治疗后血清NO水平明显升高（P＜0．01）,非洛地平治疗后血清NO无明显变化（P＞0．05）。结论：老年高血压病人体内（NO）水平显降低,且随病情加重而更为显。心达康治疗后（NO）水平明显升高。     

Renal failure in haemorrhagic shock in dogs: Salutary effects of the calcium entry blocker felodipine

Summary The efficacy of felodipine, a dihydropyridine calcium entry blocker to restore renal function was investigated in Wiggers model of haemorrhagic shock. Mongrel dogs were anaesthetized with sodium pentobarbital and subjected to haemorrhagic shock by allowing the animals to bleed into a reservoir. After maintaining the hypotensive state (mean blood pressure 40–45 mm Hg) for a period of 150 min, the blood was reinfused and the recovery of the various parameters were monitored for an additional 120 min. These studies were conducted in three different groups of dogs: (A) Solvent control, (B) Felodipine 0.01 mol/kg i. v., administered 10 min prior to reinfusion of the blood, and (C) Felodipine 0.01 mol/kg i. v., administered prior to haemorrhage. In all the three groups arterial blood pressure returned to similar basal levels following reinfusion. Felodipine administration prior to haemorrhage or before reinfusion (Group B and C) resulted in a 80–95% recovery in the renal blood flow, 60–65% in the glomerular filtration rate, 15–300% in the urine volume and 80–100% in the urinary sodium and potassium excretions. In the vehicle-treated control group, despite a 45% recovery in the renal blood flow, renal function was not restored following reinfusion.The observations made in these studies suggest that felodipine, an arteriolar dilator which also possesses natriuretic properties, could be clinically useful in the treatment of renal failure in haemorrhagic shock. Prevention of cellular calcium overload during ischaemia and reperfusion by this dihydropyridine derivative, may account for its ability to preserve vascular as well as tubular function. Send offprint requests to B. S. Jandhyala at the above address     

非洛地平缓释胶囊药物动力学与相对生物利用度

建立气相色谱-电子捕获法测定非洛地平血药浓度,比较国产非洛地平缓释胶囊和阿斯特拉公司缓释片的人体生物利用度,14名健康志愿者随机交叉口服两种制剂后,单剂量血浆中非洛地平浓度分别于3．07±0．92h和3．14±1．03h达到峰值4．75±1．38ng／ml和4．55±1．71ng／ml,药-时曲线下面积(AUC     

互聚物复合形成对口腔粘膜粘附片释放的影响

通过测量ＨＰＭＣ和ＣａｒｂｏｐｏＤ１９７４Ｐ在不同ｐＨ值的缓冲液中的混合溶液浊度变化的方法证实了互聚物复合形成。复合的程度在酸性ｐＨ条件下高,当两者比例为１：１时最强,然后随着ｐＨ值的长吭而减弱。以非洛地平为模型药物,采用直接压片工艺制备了口腔粘膜粘附片。体外释放实验表明,互聚物复合形成对药物的释放有很大影响,能够有效控制药物释放。粘附片中加入不同酸碱度的物质可调节药物的释放速率。聚合物间的这种特     

氯沙坦和非洛地平治疗中老年高血压合并高尿酸血症的疗效观察

[目的 ]　比较氯沙坦和非洛地平对中老年高血压合并高尿酸血症的疗效。　 [方法 ]　 60例中老年高血压合并高尿酸血症患者随机分成两组 ,分别服用氯沙坦 (氯沙坦组 ,n =3 0例 )和非洛地平 (非洛地平组 ,n =3 0例 ) ,分别测定两组患者治疗前后的血压、2 4h动态血压、血尿酸、空服血糖、血脂和肝肾功能。　 [结果 ]　氯沙坦和非洛地平均有明显的降压效果 (P <0 .0 1) ,两组的降压效果相似 (P <0 .0 5 ) ,但氯沙坦降低血尿酸的效果优于非洛地平 (P <0 .0 0 1) ,对血糖、肝肾功能、血脂均无明显作用 ,未发生明显不良反应。　 [结论 ]　氯沙坦治疗中老年高血压安全、有效 ,与非洛地平相似 ,并且有降低高血尿酸作用     

银杏叶滴丸联合非洛地平治疗冠心病心绞痛的临床研究

目的探讨银杏叶滴丸联合非洛地平治疗冠心病心绞痛的有效性与安全性。方法选取滨州医学院烟台附属医院2015年12月—2017年6月收治的冠心病心绞痛患者146例,根据治疗方案的不同分成对照组(73例)和治疗组(73例)。对照组患者口服非洛地平缓释片,1片/次,1次/d。治疗组患者在对照组的基础上口服银杏叶滴丸,5丸/次,3次/d。所有患者均治疗2个月。观察两组患者临床疗效,比较治疗前后两组患者心绞痛发作频率和平均持续时间,运动耐力、血清P选择素水平、生活质量评分、心脏指标和舒张期冠状动脉血流峰值速度及不良反应情况。结果治疗后,对照组临床总有效率为84.93%,显著低于治疗组的95.89%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者心绞痛发作频率和平均持续时间均显著降低(P0.05);且治疗组患者发作频率和平均持续时间明显低于对照组患者(P0.05)。治疗后,两组患者6 min步行距离和生活质量评分均显著增加(P0.05),血清P选择素水平显著降低(P0.05);且治疗后治疗组上述指标明显优于对照组(P0.05)。治疗后,两组患者LVEF和舒张期冠状动脉血流峰值速度显著升高(P0.05),LVEDD显著降低(P0.05);且治疗组患者这些指标治疗后水平明显优于对照组(P0.05)。治疗组不良反应发生率为2.74%,明显低于对照组的13.70%,两组比较差异具有统计学意义(P0.05)。结论银杏叶滴丸联合非洛地平治疗冠心病心绞痛疗效显著,不良反应发生率低,具有一定的临床推广应用价值。     

非洛地平联合倍他洛克治疗34例高血压临床效果分析

目的：探究与分析非洛地平联合倍他洛克治疗34例高血压临床效果分析。方法高血压患者34例,将其作为临床研究对象,对其采用非洛地平联合倍他洛克治疗,观察该组患者治疗前后血压及生理指标变化情况。结果该组患者在治疗1周后较治疗前相比,收缩压及舒张压有了明显下降,治疗6~12周血压下降更加显著（P〈0.05）;该组患者治疗前后血清总胆固醇（TC）、甘油三酯（TG）、血尿素氮（BUN）、血肌酐（CR）指标差异无统计学意义（P〉0.05）;该组患者治疗后较治疗前相比,血尿酸（UA）和白蛋白（Alb）有了明显下降（P〈0.05）。该组患者共34例中出现3例面红（8.82%）、4例心悸（11.76%）、3例头痛（8.82%）、3例头晕（8.82%）,因症状较轻,未采取停药处理,数天后症状自行消失。结论对于高血压患者采用非洛地平联合倍他洛克治疗后的临床效果较为显著,能够有效降低患者血压,且在治疗过程中未出现不良反应,具有一定的安全性。     

非洛地平对高血压患者血浆生长素水平和血管内皮功能的影响

目的:研究非洛地平对原发性高血压患者血浆生长素水平和血管内皮功能的影响。方法:原发性高血压患者77例,随机分为治疗组(45例)与对照组(32例),治疗组在对照组限盐、低钠饮食、适当锻炼、减轻体重、口服利尿药治疗的基础上加服非洛地平5mg,1次.d-1,治疗8wk。观察血浆生长素水平(Ghrelin)、肱动脉血流依赖性舒张功能(FMD)、一氧化氮(NO)、内皮素-1(ET-1)治疗前后变化。结果:治疗组治疗前后比较,血浆Ghrelin水平、NO、FMD明显升高,差异有统计学意义(P<0.01或P<0.05);ET-1水平降低,差异有统计学意义(P<0.01)。对照组治疗前后比较,以上指标变化无统计学意义(P>0.05)。结论:非洛地平降压治疗同时可提高血浆生长素水平,改善高血压患者的血管内皮功能。