硝苯地平对原发性高血压患者血压变异性及内皮功能的影响

目的：探讨硝苯地平对原发性高血压患者血压变异性及内皮功能的影响。方法：68例高血压患者停药2周后口服硝苯地平控释片,每日30～60mg,共4周;患者用药前后均行24h动态血压监测,采静脉血用放射免疫法测定血浆内皮素。结果：口服硝苯地平后患者的24h平均收缩压、24h平均舒张压、24h收缩压变异性、白昼收缩压变异性、内皮素含量明显下降。结论：高血压患者血压增高与内皮功能受损有关,硝苯地平有较好的降压作用,可减少血压变异性,而且可改善高血压患者的内皮功能。     

氨氯地平片与硝苯地平控释片治疗老年原发性高血压作用比较

目的比较氨氯地平片硝苯地平控释片两者对老年原发性高血压患者的疗效与不良反应。方法选取08年1月到12月在我院门诊或住院治疗的100例老年原发性高血压患者为研究对象,将入选患者随机分为硝苯地平控释片组（A组）50例,氨氯地平片组（B组）50例。采用24h动态血压检测,分别比较服用硝苯地平控释片与氨氯地平片4周后的疗效与不良反应。结果两种药物都能有效控制24h平均血压,白天平均血压和夜间平均血压;不良反应都较轻微,不影响治疗过程。结论硝苯地平控释片与氨氯地平片治疗老年性轻、中度高血压是有效、安全的。     

硝苯地平控释片与苯磺酸氨氯地平片对老年单纯性收缩期高血压疗效比较

目的 观察硝苯地平控释片与苯磺酸氨氯地平片对老年单纯性收缩期高血压的临床疗效比较.方法 将老年单纯性收缩期高血压患者71例随机分组为观察组和对照组,其中对照组35例给予硝苯地平控释片30mg口服,每日1次;观察组36例给予苯磺酸氨氯地平片5毫克口服,每日1次.连续服药四周为1疗程;疗程结束后观察两组患者的疗效.结果 对照组临床症状总有效率为94.4％,观察组为93.3％;两组患者服药后不同时间点收缩压值无显著性差异,结论 苯磺酸氨氯地平片能较快降低血压,而硝苯地平控释片降压较平稳.     

天麻钩藤饮联合硝苯地平控释片治疗高血压疗效观察

目的:观察天麻钩藤饮联合硝苯地平控释片治疗高血压的疗效.方法:对照组42例服用硝苯地平控释片30 mg·d-1.观察组42例在对照组基础上加用天麻钩藤饮400 ml·d-1.两组疗程均为8周.比较两组治疗前后24h白昼、夜间各血压均值,以及24h平均血压负荷值.结果:治疗后,两组患者24h平均血压(收缩压、舒张压)、白昼血压(收缩压、舒张压)、夜间血压(收缩压、舒张压)、血压负荷值(收缩压、舒张压)均较治疗前明显下降(P＜0.05),且治疗后观察组各项指标与对照组相比,差异有统计学意义(P＜0.05).两组均未发生严重不良反应.结论:天麻钩藤饮联合硝苯地平控释片能有效治疗高血压.     

硝苯地平控释片对老年冠状动脉粥样硬化患者血压变异性影响研究

目的:评价硝苯地平控释片用于治疗老年冠状动脉粥样硬化患者血压变异性(blood pressure variability,BPV)的影响。方法:选取2013年1月—2014年1月间诊治的老年冠状动脉粥样硬化患者89例,将其分为对照组(44例)和观察组(45例),对照组患者均给予阿托伐他汀和抗血小板凝聚及对症支持等药物治疗,观察组患者在对照组治疗基础上均给予硝苯地平控释片治疗;两组患者治疗1周,监测24 h动态血压,比较治疗前后各BPV指标,即24 h收缩压变异(24 h SSD),白昼收缩压变异(d SSD),夜间收缩压变异(n SSD),24 h舒张压变异(24 h DSD),白昼舒张压变异(d DSD),夜间舒张压变异(n DSD),收缩压(SBP)和舒张压(DBP)变化情况。结果:观察组患者治疗后收缩压变异性指标(24 h SSD、d SSD、n SSD)均明显低于治疗前和对照组治疗后;两组患者治疗后各变异性指标经比较其差异有统计学意义(P<0.05);两组患者舒张压各变异性指标(24 h DSD、d DSD、n DSD)经比较其差异无统计学意义(P>0.05);观察组患者治疗后收缩压较治疗前明显下降(P<0.05),而对照组患者治疗前后收缩压和舒张压经比较其差异无统计学意义(P>0.05)。结论:监测血压变异性,控制24 h血压值对老年冠状动脉粥样硬化患者合理使用硝苯地平控释片具有重要临床意义。     

国产硝苯地平控释片降压效果动态血压分析

目的:观察国产硝苯地平控释片的降压效果。方法:82例原发性高血压(EH)患者每天服用国产硝苯地平控释片30～60mg,疗程4～8周,均以24 h动态血压作为监测及评价方法。结果:24 h收缩压和舒张压均明显下降(P<0.01),收缩压谷峰比=89%,舒张压谷峰比=82%,对夜间血压不产生过度降压作用,对血糖、血脂、血尿酸无影响,不良反应发生率低。结论:每日服用30～60 mg国产硝苯地平控释片对EH有24 h平稳降压作用。     

硝苯地平控释片对老年原发性高血压患者血压变异性及血清胱抑素C水平的影响

目的：观察硝苯地平控释片（拜新同）对老年原发性高血压患者血压变异性（ BPV）及血清胱抑素C （ Cys-C）水平的影响。方法选取医院老年原发性高压患者62例,随机分为对照组30例及治疗组32例,治疗组予硝苯地平控释片治疗;对照组给予安慰剂作为对照。用药后第2周末做动态血压监测及检测血清胱抑素C的含量,观察BPV及其对早期肾功能的影响。结果治疗组的收缩压变异性和舒张压变异性均较对照组有明显下降,血清Cys-C含量明显降低,差异均有统计学意义（ P＜0.05）。24h血压变异性与血清Cys-C含量呈显著正相关,血压变异性与高血压性肾脏损害密切相关。结论硝苯地平控释片可有效降低老年原发性高血压患者的血压变异性,同时降低血清Cys-C水平,对肾脏具有一定的保护作用。     

苯磺酸氨氯地平与硝苯地平治疗原发性老年高血压患者的疗效比较

目的:观察苯磺酸氨氯地平与硝苯地平治疗原发性老年高血压患者的临床疗效和安全性。方法:160例原发性老年高血压患者按抽签法随机均分为A组和B组。A组患者给予苯磺酸氨氯地平片5 mg,口服,qd;B组患者给予硝苯地平控释片30 mg,口服,qd。两组患者用药时间均为早上6点至8点,疗程均为12个月。观察两组患者的临床疗效,治疗后的动态血压及不良反应发生情况。结果:A组患者总有效率显著高于B组,不良反应发生率显著低于B组,两组比较差异均有统计学意义(P<0.05);治疗后除A组患者夜间舒张压显著低于B组患者外(P<0.05),两组患者白天、24 h的动态血压及夜间收缩压、动脉压、心率比较差异均无统计学意义(P>0.05)。结论:在老年高血压长期降压用药方面,硝苯地平控释片与苯磺酸氨氯地平片的疗效与安全性均较好,实际选用时患者可根据自身情况择优选择,如夜晚舒张压高的患者可优先选择苯磺酸氨氯地平片。     

对硝苯地平控释片长效降压效果的评价

目的:评价硝苯地平控释片的长效降压效果。方法:对37例轻、中度原发性高血压患者分三部分进行评价(比较自身交叉服硝苯地平普通片与控释片的12小时静态降压效果;比较服药前后即第1天及第7天硝苯地平控释片的24h动态血压;比较硝苯地平控释片及氨氯地平的24h动态血压,计算T/P比值)。结果:普通片服后1h即出现比控释片明显的降压效果,但仅维持6h,而服控释片降压效果可维持12h以上。服硝苯地平控释片后1天及连服7天的24h动态血压监测结果显示均能明显降压,并持续24h,收缩压下降比舒张压更明显,并且在服后3h奏效。在T/P比值方面,与氨氯地平比较,虽然均>50％,但在收缩压方面,硝苯地平稍高于氨氯地平(分别为87％和74％),而舒张压则前者低于后者(分别为62％和81％)。结论:硝苯地平控释片的降压作用长达12h以上,轻、中度高血压患者一天只需服用1～2次。     

阿折地平和苯磺酸氨氯地平片对老年轻中度原发性高血压动态血压的影响

目的比较阿折地平片和苯磺酸氨氯地平片对老年轻中度原发性高血压患者血压和血压变异性（BPV）的影响。方法将60例老年轻中度原发性高血压患者随机分为2组,每组30例,分别服用阿折地平片（8mg／d）和苯磺酸氨氯地平片（5mg／d）12用,分别监测患者治疗前后24h动态血压的变化,比较两种药物对血压和BPV的影响。结果与治疗前比较,阿折地平和苯磺酸氨氯地平片治疗后均能有效地降低24h收压缩（SBP）、24h舒张压（DBP）、24hSBPV和24hDBPV,差异均有统计学意义（P〈0．05）。治疗后,阿折地平片和苯磺酸氨氯地平片在降低24hSBP和24hDBP的疗效差异无统计学意义（P〉0．05）：但在控制BPV方面,阿折地平片优于苯磺酸氨氯地平片（P〈0．05）。结论阿折地平片和苯磺酸氨氯地平片均是理想的控制血压和BPV的长效钙离子拮抗剂,阿折地平片在控制BPV方面优于苯磺酸氨氯地平片,更适用于老年轻中度原发性高血压患者。     

非洛地平缓释片与尼群地平片治疗高血压病的疗效比较

目的：比较非洛地平缓释片与尼群地平片治疗高血压病的疗效。方法：轻、中度高血压病病人１６２例,其中９８例（男性６７例,女性３１例,年龄５１ａ±ｓ６ａ）用非洛地平缓释片５～１０ｍｇ,ｐｏ,ｑｄ×４ｗｋ治疗。另６４例（男性４７例,女性１７例,年龄５０ａ±８ａ）用尼群地平片１０ｍｇ,ｐｏ,ｂｉｄ或ｔｉｄ×４ｗｋ治疗。结果：非洛地平缓释片组总有效率９５％,与尼群地平片组（８１％）相比,差别有非常显著意义（Ｐ＜０．０１）。不良反应发生率非洛地平缓释片组１５％,与尼群地平片组（２０％）比较,差别有显著意义（Ｐ＜０．０５）。结论：非洛地平缓释片对高血压病的疗效显著而又安全,优于尼群地平片。     

The comparative bioavailability of an extended-release niacin and lovastatin fixed dose combination tablet versus extended-release niacin tablet, lovastatin tablet and a combination of extended-release niacin tablet and lovastatin tablet

Lovastatin and extended-release (ER) niacin in a fixed dose combination (Advicor) is approved for the treatment of dyslipidemia. Since both drugs are extensively metabolized, this study investigated the bioavailability and pharmacokinetics of their co-administration following single-dose administration. In a 4-way crossover study 40 subjects received: two 1000/20 Advicor tablets (ADV), two 1000 mg niacin ER tablets (NSP), two 20mg lovastatin tablets (Mevacor; MEV), and two niacin ER 1000 mg tablets with two lovastatin 20mg tablets (NSP+MEV). Plasma was assayed for niacin, nicotinuric acid (NUA), lovastatin, lovastatin acid and HMGCoA reductase inhibition. Urine was assayed for niacin and its metabolites, NUA, N-methylnicotinamide and N-methyl-2pyridone-5-carboxamide. Least square mean ratios and 90% confidence intervals for C(max) and AUC((0-t)) were determined for NSP+MEV versus MEV or NSP, ADV versus MEV or NSP, and ADV versus NSP+MEV. Co-administration of niacin and lovastatin did not significantly influence C(max) and AUC((0-t)) of lovastatin, niacin, NUA and total urinary recovery of niacin and metabolites. A 22 to 25% decrease in lovastatin acid C(max) was observed while lovastatin acid AUC((0-t)) was not affected. The HMGCoA reductase inhibition C(max) and AUC((0-t)) were not affected indicating that the difference in lovastatin acid C(max) was not clinically relevant.     

Vardenafil orodispersible tablet

Vardenafil orodispersible tablet (ODT) is a supralingual formulation of vardenafil that is available for the on-demand treatment of erectile dysfunction. The pharmacokinetics of vardenafil ODT are not equivalent to those of the vardenafil film-coated tablet in that the ODT formulation provides consistently greater vardenafil systemic exposure. Therefore, the two formulations are not interchangeable. The efficacy of on-demand vardenafil ODT 10 mg was established in the POTENT I and II studies, which were 6-week, randomized, double-blind, multinational trials in men with erectile dysfunction of at least 6 months duration. In both trials, vardenafil ODT improved erectile function significantly more than placebo, as indicated by International Index of Erectile Function-Erectile Function subscale scores at week 12 and overall erection success rates during treatment according to responses to questions 2 and 3 of the Sexual Encounter Profile (coprimary endpoints). In a pooled analysis of both trials, vardenafil ODT improved erectile function regardless of age, severity of erectile dysfunction at baseline or the presence or absence of underlying medical conditions. Vardenafil ODT was generally well tolerated in clinical trials, including in men aged ≥65 years, and adverse events were mostly mild or moderate in severity.     

Fentanyl buccal tablet

Studies of populations with chronic cancer pain have shown a high prevalence of breakthrough pain (BTP), defined as transitory, severe flares of pain that occur on a background of otherwise controlled, persistent pain. High BTP prevalence rates have also been reported in patients with chronic noncancer pain, although data in these patient populations are more limited. The incidence of BTP appears to be associated with progression of chronic disease, with more than 80% of patients reporting BTP with far-advanced, end-stage cancer and noncancer terminal conditions (1). The most widely accepted therapeutic approach for the management of BTP involves use of short-acting opioids taken as needed in addition to the around-the-clock opioid regimen being used for the continuous component of the persistent pain syndrome. For some patients, an optimal treatment outcome for BTP may be unattainable because of a mismatch between the time course of the BTP episode and the onset of analgesia of short-acting opioids. Breakthrough pain typically reaches peak intensity within a few minutes, whereas the onset of analgesia with traditional, orally administered short-acting opioids is between 30 and 60 minutes (2-7). Consequently, treatment outcomes for BTP are likely to be improved with agents that have a more rapid onset of analgesia. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl indicated for the management of BTP in patients with cancer who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. The FBT formulation uses OraVescent (Cephalon, Inc., Frazer, PA, USA) drug delivery technology to provide rapid absorption of fentanyl through the buccal mucosa. In pharmacokinetic studies in healthy volunteers, FBT demonstrated high, early systemic absorption. In addition, FBT delivered a larger proportion of the fentanyl dose transmucosally and produced a greater early systemic exposure than oral transmucosal fentanyl citrate (OTFC), which is also indicated for the management of BTP in opioid-tolerant cancer patients. A number of short-term studies have evaluated the efficacy, safety and tolerability of FBT in the management of BTP in opioid-tolerant patients with chronic pain. All these studies included an open-label dose-titration phase prior to randomized, placebo-controlled, double-blind treatment. Pain Intensity of a BTP episode was measured using an 11-point scale (0 = no pain, 10 = worst pain), and the primary outcome measure was the Summed Pain Intensity Difference (SPID) at a specified time point. Secondary efficacy measures included Pain Relief, Pain Intensity Differences, and the proportion of BTP episodes demonstrating >or=33% and >or=50% improvement in Pain Intensity scores at each time point postdose, and the proportion of BTP episodes requiring supplemental medication. In a pivotal study of opioid-tolerant patients with cancer-related chronic pain and BTP, the primary outcome measure, SPID at 30 minutes (SPID(30)), significantly favored FBT compared with placebo (mean +/- SE: 3.0 +/- 0.12 vs. 1.8 +/- 0.18, p<0.0001). Better efficacy was also observed with FBT compared with placebo for pain relief, Pain Intensity Differences, and the proportion of episodes showing >or=33% and >or=50% improvement in Pain Intensity Scores. Treatment with FBT was generally well tolerated. Most adverse events were mild to moderate in severity and typical of those associated with opioid use (e.g., nausea, dizziness) (8). Similar results have been observed in studies of opioid-tolerant patients with BTP in association with noncancer-related chronic pain. In a study of patients with chronic low back pain, the primary outcome measure, SPID(60), significantly favored FBT over placebo (mean +/- SE: 8.3 +/- 0.66 vs. 3.6 +/- 0.57, p <0.0001). All secondary efficacy measures were similarly improved, with Pain Intensity Differences and Pain Relief scores showing significant differences versus placebo as early as 10 and 15 minutes, respectively. As in the study of cancer patients, treatment with FBT was well tolerated (9). Across all studies, there was no simple linear relationship between the effective dose of FBT and the dose of the around-the-clock opioid regimen or the previous supplemental opioid, indicating that doses of FBT should be individually titrated to effectiveness rather than calculated as a percentage of existing opioid regimens. This monograph summarizes current data on the clinical pharmacology, efficacy, safety and tolerability of FBT relating to the management of opioid-tolerant patients with BTP in association with chronic pain.     

硝苯地平缓释片与普通片治疗原发性高血压的疗效比较

目的：比较硝苯地平缓释片与普通片治疗原发性高血压的疗效。方法：用单盲、交叉对照法治疗４２例原发性高血压病人（男性２２例，女性２０例，年龄５４±ｓ７ａ）。甲组先用缓释片２０ｍｇ，ｐｏ，ｂｉｄ×１４ｄ，间隔１ｄ，改服普通片１０ｍｇ，ｐｏ，ｔｉｄ×１４ｄ，乙组服药先后次序与甲组相反，剂量相同，疗程均为２９ｄ。结果：缓释片与普通片的降压有效率分别为９８％及６４％，有明显差异（Ｐ＜０．０５），降压幅度缓释片也高于普通片（Ｐ＜０．０１），其影响病人心率加快反应显著小于普通片（Ｐ＜０．０１），其他不良反应的发生率较低，程度也较轻。结论：硝苯地平缓释片（２０ｍｇ，ｂｉｄ）较普通片（１０ｍｇ，ｔｉｄ）更高效而安全。     

罗红霉素分散片人体相对生物利用度研究

采用自身前后交叉对照试验方法以 12例男性健康自愿受试者 ,单剂量口服罗红霉素分散片和罗红霉素片 (对照药品 )进行人体生物利用度比较研究。应用高效液相色谱法 (HPL C)测定服药后 48h内的血清罗红霉素浓度。结果表明罗红霉素分散片和罗红霉素片的主要药动学参数达峰时间 Tmax分别为 1.6 7± 0 .6 0和2 .31± 0 .48h,峰值血药浓度 Cmax为 11.0 9± 1.6 8和 9.35± 1.31mg/L ,T1 / 2β分别为 19.5 9± 8.11和 17.70± 4.2 2 h。药时曲线下面积 AUC分别为 16 9.90± 6 6 .41和 142 .77± 40 .0 9mg.h/L ,经双单侧 t检验两者的 Tmax、T1 / 2β无显著性差异 (P>0 .0 5 )。罗红霉素分散片的 Cmax高于普通片 (P<0 .0 5 ) ,AUC略高于普通片 ,但无明显差异 (P=0 .2 386 )。罗红霉素分散片对罗红霉素片的平均相对生物利用度为 118.89% ,以上说明罗红霉素分散片的生物利用度略优于普通片。     

Preparation of bilayer-core osmotic pump tablet by coating the indented core tablet

In this paper, a bilayer-core osmotic pump tablet (OPT) which does not require laser drilling to form the drug delivery orifice is described. The bilayer-core consisted of two layers: (a) push layer and (b) drug layer, and was made with a modified upper tablet punch, which produced an indentation at the center of the drug layer surface. The indented tablets were coated by using a conventional pan-coating process. Although the bottom of the indentation could be coated, the side face of the indentation was scarcely sprayed by the coating solution and this part of the tablet remained at least partly uncoated leaving an aperture from which drug release could occur. Nifedipine was selected as the model drug. Sodium chloride was used as osmotic agent, polyvinylpyrrolidone as suspending agent and croscarmellose sodium as expanding agent. The indented core tablet was coated by ethyl cellulose as semipermeable membrane containing polyethylene glycol 400 for controlling the membrane permeability. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f(2)). It was found that the optimal OPT was able to deliver nifedipine at an approximate zero-order up to 24 h, independent on both release media and agitation rates. The preparation of bilayer-core OPT was simplified by coating the indented core tablet, by which sophisticated technology of the drug layer identification and laser drilling could be eliminated. It might be promising in the field of preparation of bilayer-core OPT.     

Relations between tablet properties

With the aid of simple mathematical models the relations between specific crushing strength (i.e. crushing strength divided by the breaking surface), friability and disintegration time of a tablet can be given. The friability is related to the porosity of the tablets and the specific crushing strength, independent of the process conditions. For the disintegration time two models have been used, depending on the disintegration mechanism. In the first one the disintegration time is only dependent on the porosity, in the second on the specific surface by weight of the granules of which the tablets are made. The theoretical relationships were verified for two tablet formulations, made under varying process conditions.     

氯吡格雷片联合辛伐他汀片治疗不稳定型心绞痛的临床研究

目的观察氯吡格雷片联合辛伐他汀片治疗不稳定型心绞痛的临床效果。方法选取2011年8月至2012年8月在我院治疗的不稳定型心绞痛患者92例,随机分为实验组和对照组,每组46例,对照组给予常规治疗,实验组则在常规治疗的基础上联合应用氯吡格雷片和辛伐他汀片。观察两组患者经过治疗后每周心绞痛复发的次数以及心绞痛持续的时间,同时检测对比两组患者在治疗前后血小板、三酰甘油、胆固醇的浓度变化;并对比两组患者的总体疗效及不良反应发生情况。结果治疗后,实验组每周复发心绞痛的次数以及心绞痛持续的时间显著少于对照组(P<0.05);实验组患者的血小板、三酰甘油、胆固醇的浓度均明显低于对照组(P<0.05);实验组的总体有效率显著高于对照组(91.30%vs.71.74%,P<0.05),两组均发生1例呕吐。结论氯吡格雷片联合辛伐他汀片治疗不稳定型心绞痛临床疗效显著,且安全性高。