别嘌醇片的人体相对生物利用度

目的评价两种别嘌醇片剂的生物利用度。方法20名健康志愿者,进行随机2周期交叉实验,采用HPLC-UV法测定人血浆中别嘌醇的浓度并计算药动学参数及生物利用度。结果受试剂与参比剂的药?时曲线下面积(AUC0-8)为(5·34±0·74)和(5·64±0·87)μg·h-1·ml-1,峰浓度(Cmax)分别为(2·03±0·42)和(1·99±0·39)μg/ml。达峰时间(Tmax)分别为(1·36±0·58)和(1·64±0·67)h。别嘌醇受试剂的相对生物利用度(F)为(97·9±16·9)%。InAUC0-t、InCmax经方差分析后无显著性差异(P>0·05);AUC0-t、Cmax经双单侧t检验有显著性差异(P<0·05),Tmax经非参数法检验无显著性差异(P>0·05)。结论两制剂具有生物等效性。     

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout

Summary The objectives of this study were to establish if, and to what extent, benzbromarone affects allopurinol/oxypurinol kinetics, and to compare the uric acid lowering capabilities of Allomaron^® (allopurinol 100 mg plus benzbromarone 20 mg) with the effects of allopurinol alone in patients with confirmed gout.We studied 14 adult men in an open randomized cross-over study. After a 14 day run-in period with Zyloprim^® (2×100 mg allopurinol tablets in the morning), the patients were randomly allocated to morning doses of either Allomaron^® (2 tablets) or Zyloprim^® (2 tablets). Seven days later cross-over was effected and the alternative treatment was taken for a further 7 days.On days 7 and 14 the patients came into hospital and venous blood samples were taken over 24 h for allopurinol and oxypurinol assays by HPLC. Serum uric acid was determined on days -14, 1, 7, and 14.Benzbromarone lowered plasma oxypurinol concentrations (Allomaron^®/Zyloprim^® mean ratio of AUC₀₂₄ was 59%; 95% confidence interval 54–64%), but did not affect plasma allopurinol concentrations.Despite this pharmacokinetic interaction of benzbromarone with allopurinol, resulting in lower plasma concentrations of oxypurinol, Allomaron^® was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone.     

长期服用别嘌醇片与别嘌醇缓释微丸胶囊对高尿酸血症大鼠肝脏作用的对比实验研究

目的考察长期(3个月)应用别嘌醇缓释微丸胶囊(奥迈必利)对高尿酸血症大鼠肝脏功能和组织结构的影响。方法试验大鼠分为正常对照组、高尿酸血症模型组、别嘌醇缓释微丸胶囊治疗组(低、高剂量)、别嘌醇片治疗组(低、高剂量)。除正常对照组以外,其余各组采用腺嘌呤和乙胺丁醇连续灌胃3周,3周后改为隔日1次的方法,共3个月造成大鼠持续性高尿酸血症。药物治疗组在造模的同时,灌胃给予别嘌醇缓释微丸胶囊或别嘌醇片,在实验3个月末,检测大鼠血尿酸含量、肝脏病理结构、反映肝功能的主要酶(丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶)的活性和肝脏指数(%)的改变。结果与正常对照组比较,高尿酸痛风模型大鼠血尿酸水平显著增高(P<0.05);天冬氨酸转氨酶活性显著增高、碱性磷酸酶活性显著降低(P<0.05);肝脏指数增高、肝脏组织结构发生病理改变。与高尿酸血症模型大鼠比较,长时间服用别嘌醇缓释微丸胶囊和别嘌醇片均可降低高尿酸血症大鼠血尿酸水平,缓解高尿酸大鼠的肝脏组织结构损伤,其中别嘌醇缓释微丸胶囊高剂量时作用显著(P<0.05);别嘌醇缓释微丸胶囊和别嘌醇片均可降低高尿酸血症大鼠天冬氨酸转氨酶活性、增高碱性磷酸酶活性,其中别嘌醇缓释微丸胶囊高剂量时升高碱性磷酸酶的作用显著(P<0.05);别嘌醇缓释微丸胶囊和别嘌醇片均可降低痛风大鼠肝脏指数,其中别嘌醇缓释微丸胶囊低剂量时作用显著(P<0.05)。结论长期应用别嘌醇缓释微丸胶囊(奥迈必利)可有效降低高尿酸血症大鼠的血尿酸水平、改善肝脏功能,保护肝脏组织结构,其作用优于相当剂量的别嘌醇片。     

Effect of amlodipine,lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

BackgroundExposure to chemotherapeutic agents such as acetaminophen may lead to serious liver injury. Calcium deregulation, angiotensin II production and xanthine oxidase activity are suggested to play mechanistic roles in such injury.ObjectiveThis study evaluates the possible protective effects of the calcium channel blocker amlodipine, the angiotensin converting enzyme inhibitor lisinopril, and the xanthine oxidase inhibitor allopurinol against experimental acetaminophen-induced hepatotoxicity, aiming to understand its underlying hepatotoxic mechanisms.Material and methodsAnimals were allocated into a normal control group, a acetaminophen hepatotoxicity control group (receiving a single oral dose of acetaminophen; 750 mg/kg/day), and four treatment groups receive N-acetylcysteine (300 mg/kg/day; a reference standard), amlodipine (10 mg/kg/day), lisinopril (20 mg/kg/day) and allopurinol (50 mg/kg/day) orally for 14 consecutive days prior to acetaminophen administration. Evaluation of hepatotoxicity was performed by the assessment of hepatocyte integrity markers (serum transaminases), oxidative stress markers (hepatic malondialdehyde, glutathione and catalase), and inflammatory markers (hepatic myeloperoxidase and nitrate/nitrite), in addition to a histopathological study.ResultsRats pre-treated with amlodipine, lisinopril or allopurinol showed significantly lower serum transaminases, significantly lower hepatic malondialdehyde, myeloperoxidase and nitrate/nitrite, as well as significantly higher hepatic glutathione and catalase levels, compared with acetaminophen control rats. Serum transaminases were normalized in the lisinopril treatment group, while hepatic myeloperoxidase was normalized in the all treatment groups. Histopathological evaluation strongly supported the results of biochemical estimations.ConclusionAmlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.     

别嘌呤醇治疗急性脑梗死伴高尿酸血症的临床效果

目的：探讨别嘌呤醇治疗急性脑梗死伴高尿酸血症的临床效果。方法选取2013年10月~2014年10月本院收治的80例急性脑梗死伴高尿酸血症患者作为研究对象,随机分为对照组和观察组,各40例。对照组给予抗凝、抗血小板聚集等对症治疗,观察组在对照组的基础上给予别嘌呤醇,比较两组治疗前后的血清尿酸水平、神经功能缺损评分以及临床效果。结果两组治疗后的血清尿酸水平与神经功能缺损评分显著低于治疗前,差异有统计学意义(P<0.05)。观察组治疗后的血清尿酸水平与神经功能缺损评分显著低于对照组治疗后,差异有统计学意义(P<0.05)。观察组的总有效率为92.5%,显著高于对照组的75.0%,差异有统计学意义(P<0.05)。结论别嘌呤醇能够明显降低急性脑梗死伴高尿酸血症患者的血清尿酸水平,改善患者的神经功能缺损症状,值得临床推广应用。     

别嘌醇干预对急性冠状动脉综合征患者高尿酸血症、高脂血症的影响

目的探讨别嘌醇干预对急性冠状动脉综合征患者高尿酸血症、高脂血症的影响。方法将急性冠状动脉综合征患者80例随机分为治疗组和对照组各40例。观察组在按冠心病二级预防的基础上加用别嘌醇100mg口服,每天3次;对照组按冠心病二级预防治疗。治疗后观察2组患者尿酸及血脂变化,并观察其预后。结果治疗组治疗后尿酸(UA)、三酰甘油(TG)、总胆固醇(CHO)、低密度脂蛋白(LDL)明显改善,且低于对照组,差异均有统计学意义(P<0.01)。治疗组临床并发症发生率低于对照组,预后优于对照组,差异均有统计学意义(P<0.05)。结论高尿酸血症、高脂血症对急性冠状动脉综合征患者有很重要的影响,对急性冠状动脉综合征伴高尿酸血症、高脂血症患者应进行积极治疗。     

后适应对大鼠脑缺血神经细胞凋亡和内皮型一氧化氮合酶与诱导型一氧化氮合酶的影响

目的：研究缺血耐受（后适应和预适应）对脑缺血再灌注神经细胞凋亡及内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）蛋白表达的影响。方法：50只雄性SD大鼠随机分为假手术组（sham）、脑缺血再灌注模型组（MCAO）、预适应组（MCAO＋preconditioning）、后适应组（MCAO＋postconditioning）和尼莫地平组（MCAO＋nimodipine），每组10只大鼠。预适应组大鼠在MCAO前24h，双侧颈总动脉夹闭2min，再灌注20min，循环两次。后适应组大鼠在脑缺血再灌注开始时，再灌注20s，栓塞20s，循环3次。大鼠大脑中动脉阻断1．5h，再灌注24h。用TUNEL法和免疫组化染色法分别检测缺血半暗带凋亡细胞和iNOS、eNOS蛋白表达。结果：与MCAO组比较，后适应组大鼠脑缺血半暗带的凋亡细胞显著减少，eNOS蛋白表达显著增加，iNOS蛋白表达显著减少，差异有统计学意义（P〈0．05）。结论：缺血后适应能诱导脑缺血耐受，对脑缺血／再灌注损伤产生保护作用，其保护作用与促进eNOS蛋白的表达，抑制iNOS蛋白的表达有关。     

尼莫地平治疗冠心病心绞痛36例临床疗效观察

我们应用口服国产尼莫地平(NMP)治疗冠心病心绞痛36例,临床观察提示NMP控制心绞痛发作总有效率为88.％;ECG心肌缺血改善率为80.6％,对高血脂病人有降血脂作用,对合并高血压者有降压作用。NMP副作用轻微,长期服用安全范围大,有一定的实用价值。     

参麦注射液治疗冠心病心绞痛的疗效观察

目的观察参麦注射液治疗冠心病心绞痛的临床疗效。方法将90例稳定型心绞痛患者随机分为治疗组和对照组,各45例。2组均给予常规治疗,治疗组另以参麦注射50ml加入5%葡萄糖或生理盐水250ml中静脉滴注,每天1次,连用10d为1个疗程。治疗后比较2组疗效及不良反应。结果临床疗效：治疗组显效率和总有效率分别为40.0%和91.1%,均高于对照组的20.0%和66.7%,差异均有统计学意义（P〈0.01或P〈0.05）。心电图疗效：治疗组总有效率为84.4%高于对照组的62.2%,差异有统计学意义（P〈0.05）。2组均未见明显不良反应。结论参麦注射液是治疗冠心病心绞痛的有效药物。     

丹参酮ⅡA磺酸钠注射液辅助治疗冠心病不稳定型心绞痛疗效观察

目的：观察丹参酮ⅡA磺酸钠注射液辅助治疗冠心病不稳定型心绞痛的临床疗效。方法：将84例冠心病不稳定型心绞痛患者随机分为治疗组与对照组,每组42例,对照组患者采用常规药物治疗;治疗组患者在常规治疗基础上加用丹参酮ⅡA磺酸钠注射液40mg,静脉点滴,1次/d,疗程均为2周。结果：治疗组患者心绞痛症状及心电图改善情况均优于对照组,差异均具有统计学意义（χ2=5.38,P〈0.05;χ2=8.42,P〈0.05）。结论：丹参酮ⅡA磺酸钠注射液辅助治疗冠心病不稳定型心绞痛的临床疗效显著,优于常规治疗方案。     

丹红注射液治疗182例冠心病心绞痛的疗效观察

目的探讨丹红注射液对冠心病心绞痛患者的临床疗效价值。方法随机按治疗组92例和对照组90例把182例冠心病心绞痛患者分为两组,对照组给予常规静脉滴注葡萄糖、氯化钾、普通胰岛素500mL,治疗组给予5%葡萄糖液500mL加丹红注射液20mg静脉滴注,两组均为每日1次,14日为1个疗程,比较两组的疗效和不良反应。结果治疗组用药后与用药前相比,丹红注射液对心绞痛的疗效总有效率达92%,试验过程中未出现不良反应。结论丹红注射液是治疗冠心病心绞痛理想的新型中药制剂,具有较好的疗效和安全性。     

国产氯吡格雷治疗不稳定型心绞痛的疗效观察

目的评价国产氯吡格雷治疗不稳定型心绞痛（UAP）的疗效及安全性。方法 123例UAP患者按随机数字表法分为试验组61例和对照组62例。2组均给予常规治疗,试验组在常规治疗的基础上给予国产氯吡格雷75mg,每天1次;对照组在常规治疗的基础上给予进口氯吡格雷75mg,每天1次。2组均连续治疗4周,观察2组临床疗效、心电图疗效和安全性。结果试验组临床疗效总有效率为90.16%,对照组为91.94%,2组比较差异无统计学意义（P〉0.05）。试验组心电图疗效总有效率为91.80%,对照组为90.32%,2组比较差异无统计学意义（P〉0.05）。试验组不良反应总发生率为27.87%,对照组为30.65%,2组比较差异无统计学意义（P〉0.05）。结论国产氯吡格雷治疗UAP与进口氯吡格雷有相同的疗效及安全性,且价格更低,值得临床推广应用。     

葛根素对大鼠缺血心肌组织内皮素-1基因表达的影响

目的观察不同剂量葛根素预处理对垂体后叶素（Pit）诱导的心肌缺血大鼠的心肌组织内皮素-1（ET-1）mRNA表达的影响。方法 30只约200g的雄性SD大鼠随机分为3组：N组（空白对照组）、C组（缺血对照组）、P组（葛根素实验组）。其中P组又分P1、P2、P3三个亚组,分别腹腔注射不同剂量的葛根素5次;N、C组分别腹腔注射等剂量的生理盐水5次。第5次给药2h后,C、P组大鼠腹腔内注射Pit,N组则注射同剂量生理盐水;随后记录体表心电图（ECG）,并计算药物注射后J点变化的绝对值;取房室沟以下心肌组织作组织ET-1mRAN表达。结果腹腔注射Pit后15min,C组J点变化值明显大于N组（P〈0.01）;P1、P2、P3组J点变化值明显低于C组（P〈0.05）,但P1、P2、P3组间比较差异无统计学意义（P〉0.05）。C组大鼠的ET-1mRAN表达显著高于N组（P〈0.01）,P1、P2、P3组的灰度值明显低于C组,差异均有统计学意义（P〈0.05）,但P1、P2、P3组间差异无统计学意义（P〉0.05）。结论葛根素预处理后能减少Pit诱导的缺血心肌组织内ET-1mRAN表达。     

Antianginal effect of conventional and controlled release diltiazem in stable angina pectoris

Two preparations of diltiazem, controlled release (CR) given twice a day (b.i.d.) and plain given 4 times a day (q.i.d.), were compared in a multicentre, double-blind, crossover study in 41 patients with stable angina pectoris. Therapeutic efficacy was assessed with maximal exercise tests, patient recordings on nitroglycerine consumption and angina attacks. No significant differences between the CR and plain tablets were seen in any of the efficacy variables. Maximal workload significantly increased from 127 W on placebo to 146 W on CR tablets and to 147 W on plain tablets. Anginal attacks/week significantly decreased from 11.7 on placebo to 4.9 on CR tablets and to 5.0 on plain tablets. Consumption of nitroglycerine tablets/week significantly decreased from 6.3 on placebo to 2.6 and to 3.4 on CR and plain-tablets, respectively. The number or the seriousness of the adverse events did not differ between the groups. The results imply that diltiazem CR b.i.d. is equally potent and safe as conventional diltiazem q.i.d. in the control of stable angina pectoris.     

The effects of felodipine in angina pectoris

Summary The clinical response to felodipine, in addition to a beta-blocker, was evaluated and compared with placebo in this double-blind cross-over study. Twenty patients with exertional angina pectoris completed the study. Felodipine reduced the number of angina attacks and the Glyceryl Trinitrate (GTN) consumption. The median exercise capacity was increased 33% after 4 weeks' felodipine treatment compared with placebo. At maximal exercise, systolic blood pressure and rate pressure product were reduced by felodipine while no change was seen in heart rate or ST-depression. Felodipine reduced both supine and erect blood pressure. The mean supine blood pressure at rest was 138/82 mm Hg after four weeks' placebo treatment compared with 114/71 mm Hg after felodipine 5–10 mg b.i.d. Felodipine has overall a modest but significant antianginal benefit when combined with a beta-blocker.     

复方丹参滴丸与前列地尔联合治疗冠心病心绞痛疗效观察

目的观察复方丹参滴丸与前列地尔联合应用对冠心病心绞痛的治疗效果。方法 72例冠心病心绞痛患者随机分为试验组40例和对照组32例。对照组给予硝酸酯常规治疗;试验组在对照组常规治疗基础上,给予复方丹参滴丸口服,前列地尔静脉滴注,疗程5d。观察2组临床疗效。结果试验组总有效率为95.0%高于对照组的87.5%,差异有统计学意义（P〈0.05）。结论复方丹参滴丸与前列地尔联合治疗冠心病心绞痛,能改善其临床症状和心电图缺血性改变,减少心绞痛发作次数、缩短心绞痛发作时间。     

曲美他嗪联合地尔硫卓治疗心绞痛的疗效研究

目的研究曲美他嗪联合地尔硫卓治疗心绞痛的效果。方法 80例心绞痛患者,随机分为观察组与对照组,每组40例。两组患者均接受常规治疗,对照组采取曲美他嗪治疗,观察组采取曲美他嗪联合地尔硫卓治疗。比较两组治疗效果,心绞痛发作次数、发作时间,不良反应发生情况。结果观察组的总有效率95.00%高于对照组的77.50%,差异具有统计学意义(P<0.05)。观察组心绞痛发作次数显著少于对照组,心绞痛发作时间短于对照组,差异具有统计学意义(P<0.05)。观察组的不良反应发生率5.00%显著低于对照组的25.00%,差异具有统计学意义(P<0.05)。结论对于心绞痛患者运用曲美他嗪联合地尔硫卓治疗,可以有效控制病情,疗效显著,安全可靠。     

无症状心肌缺血与心绞痛患者血浆内皮素-1变化的临床研究

目的 探讨无症状心肌缺血与心绞痛患者血浆内皮素-1变化的临床意义。方法 采用放射免疫法测定ET-1含量,并查心电因及超声心动图。结果 SMI与对照组无显著差异,其病变程度与ET-1变化呈零相关,AP组ET-1明显高于对照组,其病变程度与ET-l变化呈正相关,治疗后ET-l降至正常水平,AP非发作期ET-l亦有显著差异。结论 结果显示血浆ET-1水平可能在冠心病心肌缺血类型和临床症状等方面起作用。     

抗心绞痛药雷诺嗪的研究进展

雷诺嗪(ranolazine)于2006年1月美国FDA批准上市,用于治疗慢性心绞痛.它是一种脂肪酸部分氧化抑制剂,通过改变葡萄糖和脂肪酸的代谢而发挥作用.临床研究表明,雷诺嗪单独使用或者与其他药物联合应用,可以安全有效地治疗慢性心绞痛.雷诺嗪常见的不良反应是眩晕、头痛、便秘、恶心.文中对雷诺嗪的药理作用、药动学、临床研究、药物相互作用、安全性评价等进行综述.     

Hypouricemic effect of allopurinol and the novel xanthine oxidase inhibitor TEI-6720 in chimpanzees

The hypouricemic effect of a newly synthesized xanthine oxidase / xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid, was investigated and compared with that of allopurinol in male chimpanzees (n = 3). When allopurinol (10 mg/kg) was administered orally once a day for three consecutive days, it cumulatively reduced serum urate levels by 29.7, 50.1 and 60.2%, 24, 48 and 72 h, respectively, after the initial dose. This effect was dose dependent at doses of 3 and 10 mg/kg. At 3 mg/kg, the mean serum urate levels were 3.1, 2.4, 2.5 and 2.3 mg/dl before and 24, 48 and 72 h, respectively, after the initial dose. Animals treated with 10 mg/kg of allopurinol showed serum urate levels of 3.3, 2.3, 1.6 and 1.3 mg/dl, respectively. The urate-lowering effect of TEI-6720 was then comapred with that of allopurinol at a daily dose of 5 mg/kg (n = 3). Both compounds caused striking reductions in serum and urinary uric acid levels accompanied by an increase in urinary xanthine levels. These effects of TEI-6720 were more potent than those of allopurinol. TEI-6720 reduced serum urate levels by 55.9, 69.6 and 73.6%, 24, 48 and 72 h, respectively, after the first dose, whereas, the corresponding values after allopurinol were 28.1, 41.6 and 45.1%. These results suggest that the hypouricemic effect of TEI-6720 may be more potent than that of allopurinol in the treatment of hyperuricemia and gout, and that TEI-6720 may become an effective alternative drug.