左旋氨氯地平治疗轻中度高血压疗效及不良反应的临床研究

目的:为评价左旋氨氯地平降压疗效及不良反应,并与氨氯地平相比较。方法:采用随机分组平行对照方法,将120例轻、中度高血压患者分成左旋氨氯地平组(60例),口服2.5～5mg·d~(-1)和氨氯地平组(60例),口服5～10mg·d~(-1)。观察5周。每周一次上午延迟1～4小时用药并测诊室谷值坐位血压、心率、观察不良反应。结果:5周未左旋氨氯地平与氨氯地平组治疗有效反应率分别为86.7％和83.3％,每组治疗前后比较差异非常显著(P<0.01)。组间比无显著性差异(P>0.05)。左旋氨氯地平组不良反应发生率6.7％,氨氯地平组为16.7％(P>0.05),但试验组不良反应程度更轻微。结论:左旋氨氯地平与氨氯地平治疗高血压同样有效,不良反应可能更小。     

Zero-Order Release Formulation of Oxprenolol Hydrochloride with Swelling and Erosion Control

Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower C _max, higher values of t _max, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.     

泰勒宁片和科洛曲片用于隆乳术后镇痛的比较

目的:评价泰勒宁片和科洛曲片对隆乳手术后疼痛的疗效和不良反应。方法:采用随机开放平行对照试验。共完成60例,其中A组30例予泰勒宁片,单次1片;B组30例予科洛曲片,单次1片。结果:泰勒宁片对隆乳手术后引起的中度或重度疼痛总有效率可达96.7%,科洛曲片的总有效率可达83.3%。服药后泰勒宁片组的疼痛强度差均高于科洛曲组,经统计学处理,有显著性差异(P<0.05)。不良反应发生率较科洛曲片组高。结论:泰勒宁片为中强度镇痛药,对于隆乳手术后引起的中重度疼痛有良好的镇痛效果。     

盐酸吗啡普通片及硫酸吗啡控释片在不同溶剂中溶释过程的对照研究

本文采用紫外分光光度法对国产盐酸吗啡普通片及合资厂产硫酸吗啡控释片于蒸馏水、人工胃液、人工肠液中进行体外溶出度和释放度测定。结果表明，两种片剂的溶释均符合中国药典９５版标准，控释片在人工肠液中溶释参数Ｔ５０、Ｔｄ、ｍ与在蒸馏水及人工胃液中的溶释参数差异具显著性（Ｐ＜０．０１），在人工肠液中的释放过程明显缓慢。     

Comparative effects of enoximone and theophylline on plasma catecholamines and haemodynamics in cardiosurgical patients

Summary The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n=10), 4.0 mg/kg theophylline (n=10) or saline solution (control,n=10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+ 40% in the 1st min) and a marked increase in A (approximately + 7000% in the 1st min), which still remained elevated at the end of the investigation period (+ 220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index (CI; + 35%) and a decrease in pulmonary capillary wedge pressure (PCWP; −27%), pulmonary artery pressure (PAP; −21%), RVEDV and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an increase in HR (+ 26%; arrhythmia in 3 patients), PAP (+ 22%), and RVEDV (+ 19%), while REVESV (+ 26%), MAP (−16%), CI (−14%), and RVEF (−15%) fell significantly. It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline.     

A Novel Extravascular Input Function for the Assessment of Drug Absorption in Bioavailability Studies

Purpose. Flexible parametric models describing the input process after extravascular drug administration are needed for the assessment of absorption rate and the use of population methods in bioavailability and bioequivalence studies. Methods. The oral concentration-time curve modeled as the product of the input and disposition function in the Laplace domain was obtained by numerical inversion methods for parameter estimation. The utility of the inverse Gaussian input density was examined using bioavailability data of an extended-release dosage form. Measures of rate of absorption and the cumulative absorbed amount profile were defined in terms of the estimated model parameters. Results. Accurate estimation of absorption parameters was achieved by simultaneous fitting of the extravascular and intravascular data (describing the latter by a triexponential function). The new input function allowed a direct estimation of both extent of absorption and mean absorption time. Conclusions. The findings suggest that the inverse Gaussian density is a useful input function. Its flexibility may reduce the effect of model misspecification in parameter estimation. All parameters can be readily interpreted in terms of the absorption process.     

萘普生缓释胶囊的药代动力学和生物利用度研究

目的 通过健康受试者的双交叉试验比较萘普生缓释胶囊与普通片的药物动力学和生物利用度。方法１０位健康受试者一次服用这两种制剂５００ｍｇ，在稳态试验中８位受试者接受两种制剂５天，缓释胶囊５００ｍｇ每天一次，普通片每天两次，每次２５０ｍｇ。血药浓度用ＨＰＬＣ方法测定。结果 一次服药试验证明该缓释胶囊血药浓度上升缓慢，浓度变化平稳，Ｇｍａｘ为８５．９μｇ／ｍｌ，Ｔｐｅａｋ为６．０ｈ，而普通片的Ｃｍａｘ为１４０．４μｇ／ｍｌ，Ｔｐｅａｋ为３．２ｈ，两种制剂的生物利用度相当，缓释胶囊与普通片生物等效。通过８位健康受试者交叉连续服用萘普生缓释胶囊与普通片的稳态药代动力学研究表明，到第３天给药后已达到稳态，由第５天给药后的血药浓度测定数据计算其主要的稳态药代动力学参数，缓释胶囊的峰浓度（Ｃｍａｘ）、峰谷比和波动度（ＤＦ）明显低于普通片，这些参数分别为７３，１μｇ／ｍｌ、１．４８和３７．７ｏ；而普通片的上述参数分别为 １００．８μｇ／ｍｌ、２．５１和７８．２％。结论 奈普生缓释胶囊具有缓释作用，能较好维持血药治疗浓度。     

吗啡抑制大鼠多觉型伤害性感受器持续放电

作利用复合致痛剂引起大鼠尾部皮肤多觉型伤害性感受器（ＰＭＮ）持续性放电模型，经股静脉注入吗啡（４ｍｇ／ｋｇ），显抑制ＰＭＮ持续性放电。吗啡抑制ＰＭＮ放电５０％的潜伏期为１０±４．５ｍｉｎ，抑制时程超过３０ｍｉｎ。纳络酮１ｍｇ／ｍｇ ｉｖ，可翻转吗啡的抑制作用。在慢性吗啡耐受大鼠，吗啡几乎失去其抑制作用。吗啡引起的ＰＭＮ放电数变化不呈一致关系。小剂量吗啡（１ｍｇ／ｋｇ）注入支配感受野皮肢的尾动脉     

Post-ischemic release of nucleosides and oxypurines in isolated rat hearts. Possible involvement of ventricular fibrillation

Summary In isolated perfused rat hearts global ischemia for 2, 5, and 15 min was produced. Depending on the duration of the ischemia, postischemic reperfusion led to the release of adenosine and its catabolites, and to more or less severe ventricular tachyarrhythmias. When ventricular fibrillation occurred, a highly significant increase in the purine release was observed compared with non-fibrillating hearts. Prevention of fibrillation by antiarrhythmic drugs decreased the purine release in a highly significant way. After only 2 min of ischemia, reperfusion did not lead to ventricular fibrillation. Electrical induction of fibrillation during the reperfusion in these hearts provoked the release of very high amounts of the purine compounds. A similar effect of electrically-induced fibrillation was also obtained in hearts without a previous ischemic period. The findings suggest that ventricular fibrillation is able to induce the release of purine derivatives from the heart.     

The effect of the synthetic neuroprotective dipeptide noopept on glutamate release from rat brain cortex slices

The level of spontaneous and K⁺-stimulated release of endogenous glutamate was studied in experiments on slices of brain cortex of Wistar rats. Pronounced spontaneous release of the neuromediator and its increase under conditions of stimulation were registered by high-performance liquid chromatography with electrochemical detection. The effect of the nootropic and neuroprotective dipeptide Noopept (GVS-111) on release of glutamate was investigated. The peptide in concentrations of 10^?5 and 10^?6 M caused a statistically significant decrease in spontaneous and K⁺-stimulated glutamate release. This effect could be the basis of the neuroprotective action of the peptide, suggesting that further studies of Noopept as neuroprotector are very promising.