盐酸洛非西定治疗海洛因戒断综合征的双盲对照研究

目的：就盐酸洛非西定抗阿片类戒断症状的疗效及不良反应与可乐定进行比较研究。方法：对１００例海洛因依赖者进行随机对盲的治疗共１０ｄ，两组于治疗ｄ１￣ｄ４给予充分剂量，于治疗ｄ５￣ｄ１０逐渐减量，ｄ１１停药，每日于规定时间记录戒断综合征有不良反应。结果：治疗期内戒断综合症总分急剧下降，呈明显时效关系。盐酸洛非西定改变体位时晕倒的发生率显著低于可乐定组。结论：盐酸洛非西定和可乐定抗阿片类戒断综合征疗效相     

盐酸洛非西定脱毒35例疗效评价

盐酸洛非西定是咪吐批衍生物，是a－2去甲肾上腺素能受体激动剂，可使去甲肾上腺素促神经活性降低，从而减轻或缓和阿片类成痛者的戒断症状。我所使用国产四类新药盐酸洛非西定片与盐酸可乐定（国家卫生部规定的戒毒药临床验证对照品），对60倒吸毒者进行临床双盲双模拟随机对照观察，肯定了盐酸洛非西定的脱毒效应。现报告如下：1观察对象与治疗方法1．1观察对象：本所自1997年11月19日至1997年12月13日从云南省禄丰县收治病人60例，全部为海洛因依赖者，符合ffiM－IV阿片类药物依赖的诊断标准。病人随机分为两组，其中盐酸治非西定组35…     

盐酸洛非西定片与美沙酮口服液控制阿片戒断症状的临床对照观察

目的··：了解盐酸洛非西定片（ＬＦＸ）控制阿片戒断症状的疗效。方法··：采用随机双盲方法,以美沙酮口服液（Ｍ）作为对照组,进行临床观察比较。结果··：盐酸洛非西定片能有效控制常见的戒断症状;治疗早期Ｍ组效果优于ＬＦＸ组（Ｐ＜０．０１）,随着治疗的进行,两药控制戒断症状差异无显著性（Ｐ＞０．０５）,而后期ＬＦＸ组效果优于Ｍ组（Ｐ＜０．０１）。不良反应盐酸洛非西定片组出现较多,主要表现为头晕、恶心、口干、乏力等,但随着剂量减少,不良反应也随之缓解。结论··：由于洛非西定本身不具有依赖性,因此是一种值得推广的戒毒药物。     

盐酸洛非西定对吗啡依赖动物的脱毒治疗

盐酸洛非西定是肾上腺素α２受体激动剂，作用与可乐定相似，本实验通过研究盐酸洛非西定对吗啡依赖大鼠和猴的戒断症状的抑制作用，评估其戒断治疗效果，实验结果表明，盐酸洛非西定可显著控制吗啡依赖大鼠和猴的戒断症状，效能与可乐定相似，为其临床应用提供了可靠的依据。     

十复生和洛非西定治疗海洛因依赖稽延性戒断症状对照研究

目的：探讨十复生胶囊对海洛因依赖患者临床脱毒后稽延性戒断症状的临床疗效及安全性。方法：将128例海洛因依赖患者使用美沙酮临床脱毒1周后随机分成两组（十复生和洛非西定各64例），分别给予十复生胶囊与盐酸洛非西定片治疗2周，采用海洛因稽延性戒断症状评定量表评定疗效，药物不良反应量表评定不良反应。结果：两组之间疗效存在明显差异。结论：十复生胶囊在治疗海洛因依赖患者临床脱毒后的稽延性戒断症状明显优于盐酸洛非西定片。     

服用抗精神病药物患立位血压的观察

目的通过对服用抗精神病药物患者不同体位血压的观察,以预防体位性低血压的发生。方法采用回顾性研究132例服用抗精神病药物患者坐位、卧位和立位血压的测量并进行数据处理。结果体位性低血压发生在立位的发生率为21.21%。结论临床应对服用抗精神病药物患者立位血压的测量列入常规检查。     

盐酸洛非西定片与美沙酮口服液控制阿片戒断症状的临床对？…

目的：了解盐酸洛非西定片控制阿片戒断症状的疗效。方法;采用随机双盲方法,以美沙酮口服液作为对照组,进行临床观察比较。结果;盐酸洛非西定片能有效控制常见的戒断症状;治疗早期Ｍ组效果优于ＬＦＸ组,随着治疗的进行,两药控制戒断症状差异无显著性、而后期ＬＦＸ组效果优于Ｍ组。     

盐酸奥洛他定在中国变应性鼻炎人群的非劣效临床研究设计及其定量分析*

目的:通过非劣性设计,评价盐酸奥洛他定片剂治疗变应性鼻炎的安全性和有效性。方法:以盐酸氯雷他定片为对照,采用随机、双盲双模拟、多中心、平行对照、非劣效临床研究。两组各120例。试验组早晚各1次口服盐酸奥洛他定,每次5 mg;对照组早晨服用氯雷他定片10 mg。按双模拟方法编盲,以症状体征总积分下降值为主要疗效指标,非劣效标准(δ)设为1分,疗程2周。结果:用药后2周,两组各项症状明显改善,症状体征总积分和生活质量评估等级较用药前显著下降(P<0.01);作为主要疗效指标的症状总积分差值(FAS集),组间差值95%可信区间为[-0.260,0.880],即试验组不劣于对照组(P<0.05)。对照组有效率为61.5%,不良反应发生率为9.2%;试验组有效率62.4%,不良反应发生率为5.8%,组间差异无统计学意义(P>0.05)。结论:盐酸奥洛他定治疗变应性鼻炎疗效确切,不劣于对照药氯雷他定,患者耐受性好,未发现严重不良反应。     

复方防风颗粒治疗海洛因急性戒断症状的多中心临床研究

目的:评价中药复方防风颗粒对海洛因急性戒断症状的疗效及安全性。方法:采用多中心随机双盲、双模拟阳性对照试验设计,复方防风颗粒组入组112例,完成104例,盐酸洛非西定组入组113例,完成103例。疗效评价主要指标有戒断症状总分逐日减分率,次要指标有临床疗效、HAMA量表评分。安全性指标为血、尿常规检查、血生化检查、心电图检查、生命体征测定,以及每天观察记录不良事件。结果:复方防风颗粒10d脱毒治疗显示,与盐酸洛非西定比较,两组脱毒疗效差异无统计学意义。两组的急性戒断症状量表逐日减分率、临床疗效及HAMA量表总分比较差异无显著性。复方防风颗粒组不良事件发生率显著低于盐酸洛非西定组(P<0.0001);两组不良事件严重程度、生命体征、血、尿常规检查、血生化检查、心电图检查指标比较差异无显著性。结论:复方防风颗粒治疗海洛因急性戒断症状有效,不良反应较轻。     

海洛因依赖躯体脱毒治疗方案的比较

目的··:寻找一种相对较佳的躯体脱毒治疗方案。方法·· :对符合DSM -Ⅲ -R药物依赖及阿片类戒断反应诊断标准的90例海洛因依赖者随机分成3组 ,即美沙酮替代递减法 (A组 )、阶梯治疗法 (美沙酮口服液 ,盐酸丁丙诺啡注射液和盐酸洛非西定片 ,B组 )、盐酸洛非西定递减治疗 (C组 )3组。采用双盲双模拟的给药方法 ,进行为期15d的治疗比较。戒断症状采用《戒断症状评定量表》、《汉密顿焦虑量表》和《不良反应观察量表》进行评定。结果··:A、B两组d2 -8戒断症状分值无显著性差异(P>0.05) ,C组与A、B两组d2 -8戒断症状分值有显著性差异(P<0.05)。A组后期戒断症状减分缓慢 ;C组头晕、恶心等不良反应出现较多。结论·· :阶梯治疗法 (B组 )相对较好     

Ethnic sensitivity study of fingolimod in white and Asian subjects

OBJECTIVE: The authors compared the pharmacokinetics and pharmacological effects of the immunomodulator fingolimod in healthy white and Asian subjects for potential ethnic differences. METHODS: White and Asian (Japanese) healthy subjects were demographically matched for sex, age and weight. Subjects received single 1.25 mg doses of fingolimod (6 ethnic pairs), 2.5 mg (7 pairs), 5 mg (6 pairs) or 5 mg/day for 7 days (6 pairs). The pharmacokinetics of fingolimod, major metabolites, peripheral blood lymphocyte counts and heart rate were characterized over 1 month after single-dose and 2 months after multiple-dose administration. RESULTS: There were no clinically relevant differences in the fingolimod dose Cmax or dose AUC relationships between Asian subjects (slopes 0.84 and 1.05) versus white subjects (slopes 1.13 and 1.26) after single-dose administration. During multiple-dose administration, there were no clinically relevant interethnic differences in fingolimod accumulation ratios (6.6 +/- 0.4 for whites, 7.0 +/- 0.7 for Asians), area under the concentration-time curve (390 +/- 73 versus 382 +/- 106 ng x h/ml), or elimination half-life (7.4 +/- 0.8 versus 7.9 +/- 2.0 days). The acute decrease in lymphocyte counts after single- and multiple-dose fingolimod were similar in the two ethnic groups. The lymphocyte recovery rate to baseline after a 5 mg single dose and 5 mg/day multiple dose was reduced by 36 and 15% in Asian subjects compared with white subjects. The transient, acute decrease in heart rate after the first dose of fingolimod and the subsequent return to baseline was similar in the two ethnic groups. CONCLUSION: There were no marked differences between healthy white and Asian subjects in fingolimod single-dose and multiple-dose pharmacokinetics, lymphocyte trafficking and heart rate responses.     

Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: Part 2.

Acute intravenous administration of the phytoestrogen genistein (G) blocks the gonadotropin-releasing hormone-(GnRH)-induced rise of luteinizing hormone (LH) in ovariectomized rats. The present experiments were performed to determine whether subacute administration of G or the mycoestrogens zearalenone and zearalenol would affect GnRH-induced or progesterone-induced LH secretion in ovariectomized rats. Charles River CD rats were ovariectomized and used 2 to 5 weeks later. Blood samples were obtained either via decapitation or via intraatrial cannulae three days after compounds were injected subcutaneously in sesame oil or corn oil vehicle. LH was measured by RIA. Pretreatment with estradiol benzoate suppressed LH levels at 1200 h, while G had no effect. Challenge with progesterone (8 mg/kg BW, sc) evoked LH release at 1600 h in rats pretreated with estradiol benzoate, but LH levels did not change in rats pretreated with G, zearalenone, or zearalenol. While GnRH-induced LH secretion was preserved in rats pretreated with estradiol, no LH response was detected in rats pretreated with the higher dose of G (8 mg/kg BW) or either dose of zearalenol (0.8 mg/kg BW or 8 mg/kg BW). We conclude that in the ovariectomized rat 1) subacute administration of G, zearalenone, or zearalenol do not inhibit tonic LH secretion, 2) G, zearalenone, and zearalenol do not provide "estrogenic priming" for progesterone-induced LH secretion; however, 3) G and zearalenol do block GnRH-induced LH secretion. The seemingly selective neuroendocrine effects of these naturally-occurring dietary estrogens emphasize that actions of each putative estrogen must be characterized for each "estrogenic" endpoint.     

健脑康胶囊人体耐受性试验

目的评估健康志愿者口服健脑康胶囊后的安全性。方法共32名志愿者依注册顺序分组,安慰剂对照,双盲服药。18名健康志愿者分5个剂量组分别单次口服健脑康胶囊;14名健康志愿者分2个剂量连续7d口服健脑康胶囊。结果18名单次口服试验者给药后24 h体格检查、生命体征检查未见异常,其中300 mg组(>临床推荐剂量4倍)、375 mg组(>临床推荐剂量5倍)各有1名受试者发生轻度的心电图变异,375 mg组2名受试者有轻度头痛和胃部不适。14名多剂量组受试者连续服药后未发生与健脑康胶囊相关的不良事件。结论健康人体口服健脑康胶囊剂量应低于每次225mg安全性良好。     

米非司酮及孕三烯酮治疗子宫腺肌病的临床观察

目的探讨米非司酮孕三烯酮治疗子宫腺肌病的疗效及长期用药的安全性。方法选择80例要求药物治疗的子宫腺肌病患者随机分为2组,分别予米非司酮、孕三烯酮口服。米非司酮组于月经第1天起口服米非司酮10 mg,每天1次,孕三烯酮组每次2.5 mg,每周2次,第1次于月经第1天服用,3 d后服用第2次,以后每周相同时间服用。2组患者均连续服用6个月,比较治疗前与服药6个月后痛经、闭经、胃肠道反应、肝功能、性激素水平子宫大小变化及复发情况。结果米非司酮组服药6个月后痛经症状缓解率、闭经率、血清FSH、LH、E2水平及停药后复发情况与孕三烯酮组比较差异无显著性（P〉0.05）。胃肠道反应,肝功异常发生率,血清孕激素水平,子宫大小变化情况相比,差异均有显著性（P值均〈0.05）。结论米非司酮较孕三烯酮治疗子宫腺肌病更加安全有效,且副作用少。     

奥兰替胃康片I期临床耐受性试验

 　目的：观察奥兰替胃康片（枳实总黄酮苷提取物）在健康志愿者中的安全性和耐受性。方法：单次给药组38名健康志愿者分为7个剂量组,分别给予奥兰替胃康片100,300,600,1 000,1 600,2 400和3 000 mg (1片,n=4;3片,n=4;6片,n=6;10片,n=6;16片,n=6;24片,n=6;30片,n=6)。多次给药组12名健康志愿者分为2个剂量组,分别给予奥兰替胃康片200 mg（2片,n=6）或400 mg（4片,n=6）,tid,连续给药7 d。观察受试者的临床症状和体征、生命体征、实验室检查、心电图检查、腹部彩色B超及不良事件。结果：共32名健康志愿者完成了耐受性试验。单次、多次试验均未发生严重不良事件。单次给药试验和多次给药试验中,受试者均未出现有临床意义的体格检查、实验室检查、心电图检查异常。单次给药1 000 mg组发生了5例不良事件,很可能与试验药物有关;1 600,2 400,3 000 mg组停止进行试验。多次给药试验中无不良事件发生。结论：奥兰替胃康片在100~600 mg范围内用药的安全性和耐受性良好。单次给药的最大耐受剂量为600 mg。多次给药每次200~400 mg,tid,连续7 d安全且耐受性好。推荐的II期临床试验的给药方案为每次400 mg,tid。     

129例消化性溃疡患者不同时间服用泮托拉唑钠肠溶胶囊的疗效观察

目的观察泮托拉唑钠肠溶胶囊不同时间给药对治疗消化性溃疡的疗效影响。方法将医院确诊为消化性溃疡的129例患者,用泮托拉唑钠肠溶胶囊治疗,每次40 mg,Qd,疗程均为5周,按服药时间不同分为观察组(晚上固定时间服药)与对照组(白天不固定时间服药),对比两组给药后的疗效和副作用。结果观察组疗效优于对照组,且不良反应少,差异有统计学意义(P<0.05)。结论用泮托拉唑钠肠溶胶囊治疗消化性溃疡,晚上固定时间服药比白天不固定时间服药疗效更好,副作用更少。     

Effects of repeated caffeine administration on cognition and mood

The effects of repeated caffeine administration on cognitive and mood tasks were investigated in a double-blind study of 32 young healthy adults who were randomly assigned to one of the four treatment conditions: 0, 200, 400, or 600 mg of caffeine. Subjects were tested over six alternate days; on each test day they completed various tasks after drug administration. In general, caffeine produced no significant effects on cognitive performance; the exception is that the highest dose (600 mg) reduced the speed of completion of additions relative to the other doses. Also, post-hoc analysis showed that the highest dose impaired performance of the lower caffeine users more than higher users. Mood assessment showed individuals were sensitive to the effects of caffeine but the effect did not interact with cognitive performance. The present data suggest that tolerance to the cognitive effects of caffeine does not develop with continued caffeine administration, given the limitations that the individuals tested were young healthy adults and the testing took place only over 2 weeks.     

New evidence for the selective, long-lasting central effects of the brain-targeted estradiol, Estredox

The present study examined the dose- and time-dependent central effects of an estradiol chemical delivery system cyclodextrin complex (E(2)-CDS-CD) on the reestablishment of copulatory behavior of castrated male and ovariectomized female rats with concomitant determination of the blood luteinizing hormone (LH) and E(2) levels. In orchidectomized males, Estredox, after single doses of 0.3 and 3.0 mg/kg iv, reestablished the mounting and intromission up to 4 weeks. The LH suppressive effect lasted to Day 7 and 28, respectively. After repeated administration for 10 days at a dose of 0.01mg/kg iv, significant effect was obtained by Day 14. Ovariectomized females were treated iv daily for 5 days either with E(2)-CDS-CD, estradiol benzoate (EB) or vehicle, and the lordosis quotient was determined. At a dose of 0.03 mg/kg the duration of EB's effect was 10 days shorter and only one-third of that of E(2)-CDS-CD. The LH suppression lasted to Day 18. On the other hand, after EB treatment there was no significant decrease in LH levels. The low plasma E(2) levels indicated fast rate of peripheral elimination in both males and females. The brain-targeting E(2) indicates better efficacy and increased safety in replacement therapies because of the reduced peripheral side effects.     

The bioavailability of ofloxacin from several formulations

The bioavailability of ofloxacin after a single dose of one of two tablet formulations (200 or 400 mg) or a liquid formulation (1.67 mg/ml) was investigated in 24 healthy male volunteers in an open randomized, crossover design study with a 5-day wash-out period between doses. Plasma concentrations of ofloxacin were determined at various times after administration by a sensitive and specific High Pressure Liquid Chromatography (HPLC) method. Ofloxacin was well absorbed after each administration, although somewhat more slowly after the tablet formulations than the solution. Mean AUC values of 31.8, 31.3, and 31.3 micrograms.hr/ml were calculated after administration of the solution, 2 x 200 mg tablets and a 400 mg tablet, respectively. Thus, the bioavailability of the tablets was in excess of 98% that of the liquid reference. Mean Cmax values of 4.4, 3.7 and 3.7 micrograms/ml were observed at Tmax values of 0.8, 1.6 and 1.8 hours after administration of the solution, 2 x 200 mg tablets and a 400 mg tablet, respectively. The drug was well tolerated and no adverse effects necessitating subject withdrawal were noted during the study.     

国产甲磺酸托烷司琼正常人体耐受性试验

目的考察国产甲磺酸托烷司琼正常人体耐受性。方法24名健康志愿者,随机分为7组,分别参加单次静脉注射甲磺酸托烷司琼3,6,12mg组以及分别po3,6,12,24mg*d-1,连续5d。结果2种剂型在所试剂量范围内都可耐受。对于神经系统、心血管、肝肾功能及实验室指标无明显影响;≤6mg