Aspirin in the prevention of cardiovascular events in patients with diabetes

Diabetes imparts a substantial increased risk for cardiovascular disease-related mortality and morbidity. Because of this, current medical guidelines recommend prophylactic treatment with once-daily, low-dose aspirin (acetylsalicylic acid) for primary and secondary prevention of cardiovascular (CV) events in high-risk patients. However, only modest reductions in CV events and mortality have been observed with once-daily aspirin treatment in patients with diabetes, including patients with a previous CV event, perhaps because of disparity between aspirin pharmacokinetics and diabetes-related platelet abnormalities. Once-daily aspirin irreversibly inactivates platelets for only a short duration (acetylsalicylic acid half-life, approximately 15–20 minutes), after which time newly generated, active platelets enter the circulation and weaken aspirin’s effect. Platelets from patients with diabetes are more reactive and are turned over more rapidly than platelets from normal individuals; the short inhibitory window provided by once-daily aspirin may therefore be insufficient to provide 24-h protection against CV events. Alternative conventional aspirin regimens (e.g. higher daily dose, twice-daily dosing, combination with clopidogrel) and newer formulations (e.g. 24-h, extended-release) have been proposed to overcome the apparent limited efficacy of conventional aspirin in patients with diabetes; however, tolerability concerns and limited clinical efficacy data need to be taken into account when considering the use of such regimens.     

左乙拉西坦缓释片在Beagle犬中的生物等效性研究

目的以Beagle犬为模型考察自制左乙拉西坦缓释片与参比缓释片(Keppra XR)在动物体内的生物等效性。方法 Beagle犬分别单剂量口服自制缓释片与参比制剂1 000mg,采用LC-MS/MS方法测定犬血浆中左乙拉西坦的浓度,通过药代动力学计算软件WinNonlin 5.2以非房室模型分别计算左乙拉西坦的药代动力学参数。结果自制缓释片与市售参比缓释片单剂量口服后,左乙拉西坦的达峰时间tmax分为1.67h和3.0h;峰浓度Cmax分别为89.50μg/ml和71.18μg/ml;消除半衰期t1/2分别为3.68h和3.50h;药时曲线下面积AUC(0-48)分别为826.57μg·h/ml和757.84μg·h/ml;药时曲线下面积AUC(0-∞)分别为826.68μg·h/ml和757.93μg·h/ml。与参比缓释片相比,自制左乙拉西坦缓释片的相对生物利用度为109.07%。结论初步判定两种制剂在犬体内具有类似的药代动力学特征和生物等效性。     

亲水凝胶骨架材料制备盐酸多奈哌齐缓释片的可行性研究

目的 采用亲水凝胶骨架材料制备盐酸多奈哌齐缓释片,并对其质量进行评价。方法 采用亲水凝胶骨架材料HPMC K100LV和K4M联用通过干法制粒工艺制备盐酸多奈哌齐缓释片,以溶出曲线相似性f2值作为评价指标,通过正交设计进行处方优化,用高效液相色谱法进行含量和杂质检测,通过加速和长期试验考察片剂稳定性。结果 以该方法制备的盐酸多奈哌齐缓释片质量稳定,具有与原研制剂一致的溶出特征。结论 以该方法制备盐酸多奈哌齐缓释片具有可行性。     

HPLC法测定氟伐他汀钠缓释片的含量

目的:建立以高效液相色谱法测定氟伐他汀钠缓释片含量的方法。方法:色谱柱为Agilent SB-C18,流动相为乙腈-0.1%磷酸(50∶50),流速为1mL·min-1,检测波长为234nm,进样量为20μL。结果:氟伐他汀钠检测浓度的线性范围为4.84~96.8μg·mL-1(r=0.9999);平均回收率为100.1%,RSD=0.9%。结论:本方法简单、快速、准确、重现性好,可用于该制剂的含量测定。     

非洛地平缓释片释放度比较

目的观察非洛地平缓释片体外释放度和治疗效果分析。方法照中国药典2000版二部和卫生部有关非洛地平质量控制标准的有关规定,采用转篮法,十六烷基三甲基溴化胺-磷酸盐缓冲液为介质,紫外分光光度法测定。结果非洛地平缓释片累积释放百分率符合H iguch i方程,释放速度符合零级模型。结论不同产品药物释放情况与临床治疗结论一致。     

Pain and the physician

Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section.     

Comparative efficacy of oral extended-release hydromorphone and immediate-release hydromorphone in patients with persistent moderate to severe pain: two randomized controlled trials

Two multicenter, randomized, double-blind, crossover studies with identical designs evaluated the efficacy of oral extended-release hydromorphone (HHER) administered q24h compared with immediate-release hydromorphone (HHIR) dosed four times daily in patients with persistent moderate to severe pain. Patients titrated to a stable HHER dose were randomized to individualized doses of HHER or HHIR for 3 to 7 days before crossover to the second treatment. Primary efficacy end point was the mean of average pain intensity (API) scores, rated on a 0- to 10-point numeric scale, over the last 2 days before the pharmacokinetics/pharmacodynamics day of each double-blind period. Difference between treatments (HHER − HHIR) in study 1 was 0.17 with a 90% confidence interval (CI) (−0.01, 0.34); in study 2, difference was 0.07 with a 90% CI (−0.12, 0.26). There were no significant differences between treatments in API scores or amount of rescue medication used at any time interval within the 24-hour dosing period. No reduction in pain control occurred in patients administered HHER at the end of the 24-hour dosing period. Most treatment-emergent adverse events were opioid-related. In these studies, HHER administered q24h and HHIR dosed four times daily provided comparable analgesia at an equivalent total daily dose.     

帕利哌酮缓释片与利培酮治疗精神分裂症阴性症状的对照研究

目的:探讨帕利哌酮缓释片与利培酮对精神分裂症阴性症状的疗效和安全性。方法:分别使用帕利哌酮缓释片与利培酮对60例以阴性症状为主精神分裂症患者治疗8周,用阳性与阴性症状量表(PANSS)、不良反应量表(TESS)分别在治疗前、治疗第4周和第8周末评定疗效和安全性。结果:研究组显效率和有效率分别为63.3%和80%,对照组分别为60%和76.7%,两组比较,差异无统计学意义(P>0.05)。两组PANSS评分治疗后均较治疗前明显下降(P<0.05),研究组阴性症状因子分在治疗4周和8周时分别为(15.40±1.04)分和(12.80±0.76)分,显著低于对照组的(20.60±1.13)分和(18.10±0.71)分,两组比较,差异有统计学意义(P<0.05);研究组第8周末PANSS总分为(42.90±0.84)分,低于对照组的(44.80±0.61)分,有统计学差异(P<0.05)。研究组的不良反应以锥体外系反应和嗜睡为主,对照组以锥体外系反应和失眠、体重增加和视物模糊为主,两组的不良反应相当,均未见严重不良反应。结论:帕利哌酮缓释片是一种安全有效的抗精神病药,能够显著改善精神分裂症的阴性症状。     

帕利哌酮缓释片治疗急性期精神分裂症患者的临床疗效比较

目的:研究帕利哌酮缓释片治疗精神分裂症急性期患者的临床疗效和安全性。方法:76例急性期精神分裂症患者随机分成两组,每组38例,治疗组服用帕利哌酮缓释片,对照组服用国产奥氮平片,分别于治疗前和治疗后04,,7,14,28,42 d评定临床疗效、社会功能及不良反应。结果:治疗组和对照组7～14 d显效率分别为89.47%和60.52%(P<0.05),治疗组和对照组14～21 d显效率分别为97.37%和78.95%。结论:帕利哌酮缓释片治疗精神分裂症急性期患者的疗效略优于奥氮平片。     

盐酸非索非那定盐酸伪麻黄碱缓释片处方工艺研究

目的对盐酸非索非那定盐酸伪麻黄碱缓释片的处方及工艺进行研究。方法采用单因素和正交设计法分别考察盐酸非索非那定层和盐酸伪麻黄碱层处方。结果确定盐酸非索非那定层中崩解剂的量,盐酸伪麻黄碱层中羟丙甲纤维素,卡波姆的量为影响片剂质量的关键因素,筛选出最佳处方。结论采用本工艺进行放大生产的产品质量符合要求。