国产法莫替丁治疗胃、十二指肠溃疡病双盲多中心的临床研究

为评价国产法英替丁(Famotidine,FT)治疗消化性溃疡的疗效和安全性,在北京和上海15所医院进行了一项多中心研究。FT的剂量为40mg/日;对照组雷尼替丁(Ramitidine,RT)为300mg/日,共完成十二指肠溃疡的疗效观察480例,胃溃疡123例,分为FT胶囊组,片剂组和RT组。经胃镜判断疗效,结果显示:FT治疗胃溃疡六周的愈合率,不论胶囊组(79％)或片剂组(86.7％)均明显高于RT组(61.3％,P<0.05)。十二指肠溃疡四周的愈合率,胶囊组为66.7％,片剂组为67.5％,与RT组(70.8％)比较无显著差别,本药无严重副作用,仅少数病人有轻度口干、便秘、头晕、失眠,与对照组相似,也未发现对肝、肾功能有毒性反应。     

左旋吡喹酮化学、药理和治疗日本血吸虫病的研究

本文报告了左旋、右旋和消旋吡喹酮的小鼠LD_(50)分别为2463、1344和2553mg/kg。右旋吡喹酮的毒性显著大于左旋与消旋吡喹酮。实验治疗证明,左旋吡喹酮是杀虫的有效成分,而右旋者则几乎无效。现场临床治疗左旋吡喹酮的剂量为单剂15和20mg/kg,治后6个月粪孵阴转率分别为86.0％和83.3％(P>0.05)。左旋和消旋均为单剂30mg/kg,治后3月和6月的阴转率,左旋分别为85.2％与87.7％,与消旋的疗效(72.1％与73.6％)比较有非常显著性差异(P<0.01)。采用左旋30mg/kg(单剂)与消旋50mg/kg(单剂)与总剂量60mg/kg(二日疗法)进行比较。治后3月粪孵阴转率分别为78.33％、70.69％与73.47％(P>0.05)。左旋20mg/kg与消旋40mg/kg(单剂),配对双盲试验,治后4月和6月,左旋组的虫卵阴转率分别为94.9％与96.3％,与消旋组(97.1％与94.0％)比较则无显著性差异(P>0.05)。病人服药后副反应轻而少。结果提示左旋吡喹酮治疗轻、中度感染者的剂量可为吡喹酮剂量的一半,疗效相似。说明该药具有高效、毒性小、安全、疗法简便的优点,有助于大规模化疗的开展。     

雷贝拉唑首次单剂量口服的抑酸效应对比研究

目的 评价雷贝拉唑(RAB)对消化性溃疡患者的抑酸效应,并与奥美拉唑(OME)、泮托拉唑(PAN)等PPI比较。方法 进行开放、对照研究。选取活动期消化性溃疡病人40例,分为3组,分别给予RAB 10 mg(n=15)、OME 20 mg(n=15)及PAN 40 mg(n=10)单剂量口服,24 h胃pH监测。结果①RAB的抑酸起效时间(115.20±15.36 min)较OME及PAN均快(P<0.05,P<0.01);②RAB组24 h胃内pH>4的总时间(11.28±3.32 h)及时间百分比(59.80％±14.2％)显著高于OME(P<0.01)及PAN(P<0.01);③RAB组夜间胃pH中位数(3.86±1.03)及夜间胃pH均值(3.01±0.65)均明显高于OME组(P<0.05;P<0.01)及PAN组(P<0.01);④RAB、OME、PAN日间 pH>4的总时间长于夜间。结论 RAB、OME及PAN均有较好的抑酸效应,三者比较,RAB抑酸起效快,抑酸持续时间长,特别是夜间抑酸效应优于OME及PAN。     

不同剂量阿托伐他汀对冠脉介入治疗前后炎症因子的影响

目的研究不同剂量阿托伐他汀(立普妥)对急性冠脉综合征(ACS)患者经皮冠脉介入治疗术(PCI)前后炎症因子的影响。方法 69例行PCI的ACS患者随机分为3组:阿托伐他汀10mg/d、20mg/d、40mg/d组,两周后行PCI术。分别测定入院、PCI术前(手术当天清晨,已治疗2周)、术后48h的高敏C反应蛋白(hs-CRP)水平。结果 3组入院时hs-CRP浓度无统计学意义(P0.05);PCI术前hs-CRP的浓度与入院相比均明显降低,40mg组降低最明显,20mg组较10mg组降低明显(P0.05)。PCI术后hs-CRP浓度较术前均升高,10mg组升高最明显,20mg组较40mg组升高明显(P0.05)。3组hs-CRP变化与血脂变化无相关性(P0.05)。阿托伐他汀40mg组、20mg组、10mg组ALT3倍患者分别为2例、1例、0,ALT升高1倍～3倍分别为9例、5例、2例,观察几周后多能恢复正常。结论 PCI术后增加血清hs-CRP水平。阿托伐他汀可减轻PCI术后炎症反应,抗炎作用呈剂量依赖性,且独立于其调脂作用。阿托伐他汀20mg、40mg短期使用是安全的。     

不同剂量辛伐他汀治疗冠心病的临床疗效观察

目的观察冠状动脉粥样硬化性心脏病患者使用不同剂量辛伐他汀的疗效、安全性、对血脂斑块生长及心血管事件的影响。方法将血脂总胆固醇(TC)≥4.68mmol/L和(或)低密度脂蛋白胆固醇(LDL-C)≥2.6 mmol/L,B超检查存在不同程度颈动脉斑块形成的临床诊断为冠心病的患者(126例)按随机原则分别入选辛伐他汀80mg组(强化治疗剂量)、40mg组与20mg组(常用处方剂量)。于服药后12周及24周复查血脂,B超复查颈动脉斑块,并对心血管事件作随访登记。结果辛伐他汀80mg、40mg与20mg均能有效地降低冠心病患者血清TC及LDL-C水平,其中80mg剂量组在降TC和降LDL-C及减少心血管事件发生率方面均明显优于20mg剂量组,40mg剂量组疗效介于两组之间,三者间均存在显著差异。80mg剂量组的颈动脉斑块缩小,而40mg剂量组及20mg剂量组无颈动脉斑块缩小。三种剂量在不良反应方面无明显差异。结论辛伐他汀强化治疗剂量在治疗冠心病方面明显优于常用处方剂量;强化治疗剂量可以逆转颈动脉斑块发展。     

卡维地洛与柳安苄心定治疗原发性高血压的对比研究

目的:比较卡维地洛(山东齐鲁制药厂)与柳安苄心定(江苏溧阳制药厂)治疗原发性高血压的疗效和安全性。方法:60例原发性高血压患者随机分为卡维地洛组(C组,n=30)和柳安苄心定组(L组,n=30)。C组给予卡维地洛20～40mg/d;L组给予柳安苄心定100～200mg/d,疗程均为4周。治疗前后分别作血尿常规、血生化及心电图检查;C组10例患者作24h动态血压监测。结果:C组与L组的降压有效率分别为73.3％和80％,无明显差异(P>0.05);不良反应均较少。C组10例作24h动态血压监测的收缩压、舒张压、平均动脉压的谷峰比率值仅为28.3％、36.4％、33.3％。结论:卡维地洛是安全、有效的降压药。     

静脉注射抑酸药物对胃内PH控制的对照研究

本文采用24小时胃内PH监测仪对确诊十二指肠溃疡的病人进行前瞻交叉对照研究,观察胃壁细胞H_2受体拮抗剂泰胃美(Tagamet,Cimetidine)和质子泵抑制剂洛赛克(Losec,Omeprazole)的抑酸效果。结果显示泰胃美1600mg静注抑酸时间为12.2±2.2小时,此期胃内PH为5.6±1.2;而洛赛克40mg分别为13.2±2.6小时和PH5.6±1.4。两药均有明显抑酸作用,使用上述剂量效果无显著性差异(P>0.05)。     

苯那普利和缓释维拉帕米对高血压患者血压及运动耐量的影响

目的：观察苯那普利和缓释维拉帕米对高血压患安静、运动血压及运动耐量的影响。方法：男性高血压患40例，于用药前、后进行活动平板试验．其中苯那普利组(1组)20例，剂量10～20mg／d，缓释维拉帕米(2组)20例，剂量120～240mg／d。结果：两药均能降低安静时血压，明显降低运动峰值血压，运动血压增高幅度，血压心率乘积也呈极显降低，并有总运动时间延长，尤以1组明显，但两药间比较无差异。结论：两药均能在心肌耗氧量减少情况下，有效降压并提高运动耐量。     

体外循环瓣膜置换术中三种不同剂量氨甲环酸对术后出血和异体输血的影响

目的评估体外循环瓣膜置换术中应用不同剂量的氨甲环酸对围术期出血和输血的影响。方法本研究为多中心、前瞻性、随机对照、双盲试验。入选126例择期行体外循环瓣膜置换术的患者,随机分为高剂量组(n=33),中剂量组(n=31),低剂量组(n=31)和空白对照组(n=31)。氨甲环酸采用负荷量加维持量的给药方式。高、中、低三个剂量组负荷量分别为30mg/kg、20mg/kg和10mg/kg麻醉诱导后20分钟输注完成;三个剂量组维持量分别为20 mg/kg/h、15和10 mg/kg/h,持续静脉泵注至手术结束。空白对照组给予等量生理盐水输注。记录术后出血量和异体血制品的输注情况,并发症和不良事件发生率等。结果术前患者一般资料和围术期临床资料4组间差异无统计学意义(P0.05)。高剂量组,中剂量组,低剂量组和空白对照组的出血量分别为(514.24±450.09)ml、(615±340.25)ml、(692.74±218.84) ml和(1057.26±437.39) ml,差异具有统计学意义(P0.05)。异体红细胞输注量分别为(2.45±2.7) 1U、(2.65±3.59) U、(2.89±2.59) U和(5.42±5.05)U,血浆输注量依次为(303.33±465.15) ml、(353.55±592.88) ml、(389.68±476.34) ml和(681.94±707.72)ml;异体血输注方面,高,中剂量组与空白对照组比较差异有统计学意义(P0.05),其余各组间比较差异无统计学意义(P0.05)。4组患者术后并发症及不良事件发生率等差异均无统计学意义(P0.05)。结论氨甲环酸可有效减少体外循环瓣膜置换术围术期的出血量且与氨甲环酸的剂量呈正相关,而未观察到严重不良反应。     

药物治疗前后Barrett食管p53、p16的表达

目的研究不同方法治疗Barrett食管(BE)患者的疗效,并通过检测治疗前后食管中p53、p16的表达改变,探索各种治疗方法产生效果的可能机制。方法BE患者75例,分为4组,(1)对照组(A组):未给予治疗。(2)抑酸药组(B组):口服奥美拉唑20mg,2/d。(3)胆汁吸附剂组(C组):口服铝碳酸镁1000mg,3/d。(4)抑酸药 胆汁吸附剂组(D组):口服奥美拉唑20mg,2/d;铝碳酸镁1000mg,3/d。治疗前、治疗后1个月及3个月后观察临床症状及内镜下表现,取食管黏膜组织标本行病理学检查,采用SABC免疫组化检测p53、p16的表达情况。结果在缓解临床症状方面,各治疗组的症状均较治疗前明显改善,与对照组相比均有统计学差异(P<0.05);各治疗组相比,症状缓解率无明显差异,无统计学差异(P>0.05)。对照组和药物治疗组的BE黏膜均未见明显缩小。各药物治疗组p16的表达无明显差异(P>0.05)。p53在治疗后与对照组相比,除C组外均有降低,有统计学意义(P<0.05)。D组的食管标本中,p53的表达显著降低。结论抑酸药和/或胆汁吸附剂不能使BE逆转,但可消除临床症状,较难改变BE食管p16的表达。抑酸药和/或胆汁吸附剂可改变BE食管p53的表达。     

Effect of single and repeated intravenous doses of omeprazole on pentagastrin stimulated gastric acid secretion and pharmacokinetics in man.

Single intravenous doses of 10, 20, 40, and 80 mg and repeated once daily intravenous doses of 10 and 20 mg omeprazole induced a powerful and long lasting inhibition of pentagastrin stimulated gastric acid secretion (PAO) in healthy male volunteers. Single intravenous doses of 10, 20, 40, and 80 mg omeprazole inhibited PAO by 30% (p less than 0.01), 45% (p less than 0.01), 61% (p less than 0.01), and 80% (p less than 0.01), respectively when measured 1.5 h after dose, and by 20% (NS), 27% (NS), 36% (p less than 0.01) and 59% (p less than 0.01), respectively when measured 24 h after dose. Six days after repeated once daily intravenous doses of 10 and 20 mg omeprazole, PAO was inhibited by 63% (p less than 0.01) and 82% (p less than 0.01), respectively when measured 1.5 h after dose, and by 32% (p less than 0.01) and 43% (p less than 0.01), respectively when measured 24 h after dose. The inhibition of PAO by 10 mg administered intravenously as a single bolus injection was comparable with the inhibition by 20 mg as a single oral dose. Repeated once daily administration of 10 mg intravenously and 20 mg orally also resulted in comparable reductions in PAO. The reduction in PAO after repeated once daily oral administration of 20 mg was comparable with the effect of a single intravenous dose of 40 mg. Terminal half lives were short, but significantly (p less than 0.05) prolonged after a single intravenous injection of 80 mg. Repeated once daily intravenous administration of 10 and 20 mg did not result in prolongation of terminal half lives. It is concluded that intravenous administration of omeprazole causes a potent and long acting inhibition of pentagastrin stimulated gastric acid secretion in man. Its potency is augmented after repeated once daily administration.     

Inhibition of histamine or allergen-induced wheals by a single dose of acrivastine, fexofenadine or cetirizine.

Certirizine, a potent H1-blocking agent, is often recommended as an emergency drug in anaphylactic reactions because of its well documented fast onset of action. In this randomized, cross-over study we compared the onset of action after a single dose of two recently introduced antihistamines, acrivastine and fexofenadine, with that of cetirizine. The inhibition of the wheal-and-flare reaction produced by skin prick test with histamine in 20 healthy volunteers and with a relevant pollen allergen in 20 atopic patients, respectively, were measured before and at regular intervals up to 60 min after the ingestion of acrivastine (8 mg and 16 mg), fexofenadine (120 mg) and cetirizine (10 mg and 20 mg). Wheal-and-flare reaction were significantly inhibited 20 min after the intake of 16 mg acrivastine in atopic patients and 30 min after intake of 8 mg acrivastine in healthy volunteers, whereas cetirizine produced a significant inhibition of the wheal-and-flare reaction within 40-60 min. No significant inhibition could be observed within 60 min after fexofenadine intake. Therefore, in clinical settings when a fast onset of the H1-blocking action is mandatory (e.g., after insect stings or for short-term prophylaxis) we recommend acrivastine.     

Acid inhibition effect of ilaprazole on Helicobacter pylori-negative healthy volunteers: an open randomized cross-over study

OBJECTIVE: The aim of this study was to evaluate the effects and safety of different doses of ilaprazole on healthy volunteers without a Helicobacter pylori infection. METHODS: A total of 12 healthy Chinese volunteers were enrolled and divided into four groups randomly, with a 5‐day treatment of oral ilaprazole 5 mg, 10 mg and 20 mg or omeprazole 20 mg, respectively. After an interval of a 14‐day washout phase, each was switched to another dose group and eventually completed all four regimens. The percentage time of intragastric pH > 4 was the major index. The polymorphisms of the metabolic enzyme CYP2C19 in these volunteers were also detected. RESULTS: The percentage time of intragastric pH > 4 in the ilaprazole 5, 10 and 20 mg groups were 80.4%, 88.1% and 91.0%, respectively, during the first 24 h, compared to that of the 20 mg omeprazole group (76.6%, P > 0.05). Ilaprazole 20 mg provided a significant higher mean 24‐h pH than that of the same dose of omeprazole both on Day 1 (7.78 vs 6.67, P < 0.01) and Day 5 (7.95 vs 7.44, P < 0.05). No CYP2C19‐dependent difference or obvious adverse effect were found in any ilaprazole groups. CONCLUSION: Low dose ilaprazole offers a gastric acid inhibition comparable to a routine dose of omeprazole, and further investigations in patients with acid‐associated diseases are needed.     

Influence of aspirin on human megakaryocyte prostaglandin synthesis

Abstract: To evaluate whether currently popular aspirin regimens have an effect on the prostaglandin synthesis in human megakaryocytes we measured thromboxane B2 (TXB2) synthesis in response to thrombin stimulation in human megakaryocytes ex vivo. Human megakaryocytes were purified by Counterflow Centrifugal Elutriation from bone marrow punctures, taken from volunteers before and 2 hours after ingestion of one dose of 500 mg (n = 4), 80 mg (n = 4) or 40 mg (n = 2) aspirin. Subsequently, megakaryocytes were purified before and 12 h after ingestion of 80 mg (n = 3) aspirin twice daily for 1 week and 12 h after 500 mg (n = 3) aspirin. On average, 140 ± 102 × 10³ (mean ± 1 SD) megakaryocytes were recovered. We found that aspirin inhibits megakaryocyte cyclooxygenase in a dose-dependent manner. Two hours after 500 mg of aspirin, TXB2 synthesis in megakaryocytes was inhibited by 96.8 ±2%, whereas one dose of 80 and 40 mg aspirin showed an inhibition of 79.4 ± 13.7% and 80 ± 6.2% respectively. However, the inhibition of TXB2 synthesis seems not to be long-lasting since, 12 h after the ingestion of aspirin, an increase of megakaryocyte TXB2 production could be observed which reached significance after the 500 mg aspirin dosage (p < 0.048). We conclude that human megakaryocyte cyclooxygenase is sensitive to aspirin inhibition and that low doses of aspirin (40 and 80 mg) enter the systemic circulation and are able to inhibit megakaryocyte cyclooxygenase, but this inhibition is incomplete and megakaryocyte cyclooxygenase seems to recover within 12 h after ingestion of aspirin.     

Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers. Inhibition of pressor response to exogenous angiotensin I and II

BACKGROUND. The purpose of the present study was to assess the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy male volunteers. METHODS AND RESULTS. In the first study (single-dose study), eight volunteers were included in a 2-day protocol repeated four times at 1-week intervals. In each phase, a different dose of drug (2.5, 5, 10, 20, or 40 mg) or placebo was given. The peak systolic blood pressure response to a test-dose of angiotensin I was determined serially before and after oral administration of DuP 753 by continuously monitoring finger blood pressure using a photoplethysmographic method. DuP 753 reduced the systolic blood pressure response to angiotensin I in a dose-dependent fashion. Three, 6, and 13 hours after the 40-mg dose, blood pressure response decreased to 31 +/- 5%, 37 +/- 6%, and 45 +/- 3% of the control values (mean +/- SEM, n = 7), respectively. In the second study, 29 volunteers were treated for 8 days with either a placebo or DuP 753 (5, 10, 20, or 40 mg p.o. q.d.) and challenged on the first, fourth, and eighth days with bolus injections of angiotensin II. Again, the inhibitory effect on the systolic blood pressure response to angiotensin II was clearly dose dependent. Six hours after 40 mg DuP 753, the systolic blood pressure response to the test-dose of angiotensin II was reduced to 37 +/- 7%, 40 +/- 4%, and 38 +/- 6% of baseline values (mean +/- SEM, n = 6) on days 1, 4, and 8, respectively. With this latter dose, there was still a blocking effect detectable 24 hours after the drug. Similar to angiotensin converting enzyme and renin inhibitors, DuP 753 induced a dose-dependent increase in plasma renin that was more pronounced on the eighth than on the first day of drug administration. In these normal volunteers, no consistent clinically significant side effects were observed. There was no evidence for an agonist effect. CONCLUSIONS. DuP 753 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of angiotensin II in men.     

Effect of intravenous diazepam on human lower oesophageal sphincter pressure under controlled double blind crossover conditions.

The effect of diazepam on the lower oesophageal sphincter (LOS) pressure is controversial. Therefore, a double-blind crossover study was performed on 18 healthy volunteers to determine the sphincter response to intravenous diazepam--70, 140, 280 microgram/kg, which correspond to a total dose of 5, 10, and 20 mg. respectively. After the 5 and 10 mg dose no signficant effect on LOS pressure could be observed when compared with placebo. After the 20 mg dose a significant rise in pressures (deltaPLOS) was recorded for 40 minutes with a maximum deltaPLOS of + 16.2 +/- 6.6 (mean +/- SEM) mmHg after 50 minutes (P less than 0.01) (46 +/- 1.3% increase above the basal pressure). It is concluded that diazepam does not affect lower oesophageal sphincter competence and therefore does not increase the risk of regurgitation and pulmonary aspiration in premedicated patients.     

Comparison of once-daily intravenous and oral omeprazole on pentagastrin-stimulated acid secretion in duodenal ulcer patients.

The effect of 5 days of once-daily dosing with 20 mg p.o. and 40 mg i.v. omeprazole on pentagastrin-stimulated acid secretion was studied in 8 patients with duodenal ulcer. In addition they also received a 10-mg i.v. dose on day 6 during the oral treatment period. The antisecretory effect was measured 6-7 h after dose at a time point when maximal inhibition during the dosing interval is anticipated. The median percent inhibition of peak acid output (PAO) markedly increased from 43% on day 1 to 100% on day 5 during treatment with 20 mg p.o. The first 40-mg i.v. dose produced a median inhibition of 98% of PAO already on day 1. After 5 days of dosing, the inhibition had increased to 100%. On the other hand, a 10-mg i.v. dose could essentially maintain the degree of PAO reduction reached after 5 days of oral treatment. Plasma omeprazole concentrations increased during repeated dosing both with 20 mg p.o. and 40 mg i.v.     

Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals

This study assessed whether the co-administration of ezetimibe and simvastatin would be more effective than simvastatin monotherapy in allowing high-risk patients to achieve a low-density lipoprotein (LDL) cholesterol goal of <100 mg/dl. Men and women with LDL cholesterol ≥130 mg/dl and meeting National Cholesterol Education Program Adult Treatment Panel III criteria for coronary heart disease (CHD) or CHD risk equivalent were randomized to 1 of 4 daily treatments for 23 weeks: simvastatin 20 mg (n = 253), ezetimibe 10 mg plus simvastatin 10 mg (n = 251), ezetimibe 10 mg plus simvastatin 20 mg (n = 109), and ezetimibe 10 mg plus simvastatin 40 mg (n = 97). In all groups, patients not at goal had their simvastatin doses doubled at weeks 6, 12, and/or 18, up to a maximum of 80 mg. The primary efficacy objective was LDL cholesterol goal attainment (<100 mg/dl) after 5 weeks of treatment. Ezetimibe plus any dose of simvastatin produced greater reductions in LDL cholesterol and allowed more patients to achieve goal after 5 weeks (p <0.001) and at the end of the study (p <0.001) than simvastatin 20 mg alone. At 5 weeks, 75%, 83%, and 87% of patients receiving ezetimibe plus simvastatin 10, 20, and 40 mg had LDL cholesterol <100 mg/dl compared with 46% of patients receiving simvastatin 20 mg. In patients who started on ezetimibe plus simvastatin 10, 20 and 40 mg, 33%, 22%, and 12%, respectively, required simvastatin titration during the study compared with 68% of patients who started on simvastatin 20 mg. The corresponding median simvastatin doses used were 10, 20, 40, and 40 mg, respectively. Ezetimibe plus simvastatin was well tolerated, with an overall safety profile similar to that of simvastatin monotherapy. Thus, through the dual inhibition of cholesterol absorption and synthesis, ezetimibe plus simvastatin allowed more patients to reach LDL cholesterol <100 mg/dl at a lower simvastatin dose and with fewer dose titrations than simvastatin monotherapy.     

Repeated pentagastrin-stimulated gastric acid secretory tests carried out in the evaluation of the pharmacodynamics of a new histamine H2-receptor antagonist, SK&F 93479

Single doses of 10 mg or 20 mg intravenously or 25 mg or 40 mg orally of a new histamine H2-receptor antagonist, SK&F 93479, have been administered to 31 patients with peptic ulcer disease. BAO and MAO were measured before and repeated during a 26-h period after drug administration. In a separate group of 17 patients the mean coefficients of variation of BAO and MAO measured in this manner were 53% and 20%, respectively. If this variation in the placebo group is taken into account, BAO was significantly inhibited at all dose levels during the 3rd h after dosing, and a significant effect was still seen during the 25th h after 40 mg orally with a mean reduction of 77%. Mean inhibitions of MAO during the 4th h after dosing of SK&F 93479 were significant at all dose levels, and a significant effect could still be seen during the 26th h for the two oral doses. The mean inhibitions of MAO measured during the 4th and 10th h after dosing were after 10 mg intravenously 44% and 11%, after 20 mg intravenously 59% and 11%, after 25 mg orally 57% and 21%, and after 40 mg orally 75% and 46%. The percentage inhibition of MAO during the 10th h correlated with plasma concentrations (r = 0.64, p less than 0.01). SK&F 93479 is a potent inhibitor of acid secretion with a long duration of action.     

Comparison of effects of ezetimibe/simvastatin versus simvastatin versus atorvastatin in reducing C-reactive protein and low-density lipoprotein cholesterol levels

The lowering effects of ezetimibe/simvastatin combination therapy on low-density lipoprotein (LDL) cholesterol and high-sensitivity C-reactive protein (CRP) were compared with those of simvastatin or atorvastatin monotherapy in a large cohort of patients with primary hypercholesterolemia. To compare ezetimibe/simvastatin with simvastatin, data were combined from 3 identical, prospective 12-week trials in which patients were randomized to receive placebo; ezetimibe 10 mg; ezetimibe 10 mg added to simvastatin 10, 20, 40, or 80 mg; or simvastatin 10, 20, 40, or 80 mg. To compare ezetimibe/simvastatin with atorvastatin, data were analyzed from a phase III double-blind, active-controlled study in which patients were randomized equally to receive ezetimibe/simvastatin 10/10, 10/20, 10/40, or 10/80 mg or atorvastatin 10, 20, 40, or 80 mg for 6 weeks. When averaged across doses, ezetimibe/simvastatin produced significantly greater reductions compared with simvastatin alone in LDL cholesterol (52.5% vs 38.0%, respectively) and CRP levels (31.0% vs 14.3%, respectively). At each individual simvastatin dose, co-administration with ezetimibe produced significant further CRP reductions versus simvastatin alone. Ezetimibe/simvastatin was significantly more effective at lowering LDL cholesterol than atorvastatin when pooled across doses (53.4% vs 45.3%, respectively) and in each milligram-equivalent dose comparison. Reductions in CRP of similar magnitude were observed with ezetimibe/simvastatin and atorvastatin when averaged across doses and at each milligram-equivalent statin dose comparison. In conclusion, the lipid-modulating and anti-inflammatory effects of ezetimibe/simvastatin provide additional benefits not realized by statin monotherapy alone.