tadalafil

一项对各种重组的磷酸二酯酶 (ＰＤＥ)体外研究表明 ,ＰＤＥ5分布于男性视网膜、阴茎海绵体和阴茎动脉组织中 ,礼莱公司研制的新药ｔａｄａｌａｆｉｌ(ＣｉａｌｉｓＴＭ,ＩＣ 35 1)能强效选择性抑制ＰＤＥ5 ,并通过促进ｃＧＭＰ的蓄积增强阴茎平滑肌中ＮＯ介导的应答作用。抑制其他ＰＤＥ需要较高浓度的药物。ｔａｄａｌａｆｉｌ也能增强尿道小梁平滑肌的神经松弛 ,明显增加阴茎海绵体上硝普钠诱导的ｃＧＭＰ蓄积和增强乙酰胆碱诱导的阴茎平滑肌的松弛。用健康的年轻 (19～ 4 5岁 )、老年 (6 5～ 78岁 )男女和伴有糖尿病、肾或肝不适者作为…     

治疗勃起功能障碍新药tadalafil

美国一项研究显示，由礼来公司和ICOS公司共同开发的一种新型勃起功能障碍治疗药磷酸二酯酶-5tadalafil作用可持续36小时。在一项有348例轻至重度勃起功能障碍男性参与的研究中，病人随机服用tadalafil20mg或安慰剂，结果显示，与安慰剂相比，在服药24和36小时后进行的性交成功性均得到改善，在36小时时多数男性均能成功发生2次性交，且药物不良反应发生率及严重性与安慰剂相比也未见差异。tadalafil组中5%以上男性发生头痛和消化不良。治疗勃起功能障碍新药tadalafil@刘萍 @边强…     

西地那非首次遇到市场竞争对手——tadalafil

Lilly公司现已将其 2 0 0 2年获欧共体批准的磷酸二酯酶 5 (PDE 5 )抑制剂tadalafil(Cialis)首先投放英国、德国、丹麦、芬兰、瑞典、澳大利亚和新西兰市场 ,并不久还将到欧洲其他国家销售 ,用以治疗男性勃起功能障碍。此举使辉瑞公司大名鼎鼎的PDE 5产品西地那非 (sildenafil,Viagra)在市场上遇到第一个直接对手 ,而且两者在英国的售价也相同。英国泌尿学专家认为 ,tadalafil有长达 2 4h的作用时间 ,故可在性交前 0 .5～ 12h服用 ;而西地那非等其他同类产品则必须在性交前不久服用。但这并不意味着服用tadalafil后 2 4h内一直保持着性…     

Tracleer加tadalafil改善6分钟步行距离测试

在圣迭戈召开的美国胸科学会年会上公布的PHIRST研究分析显示，肺动脉高压（PAH）患者接受20mg或40mg的Eli Lilly公司的tadalafil（Ⅰ）与一线治疗药物Actelion公司的Tracleer（bosentan，波生坦）（Ⅱ）联用，在六分钟步行距离测试（6MWD）中有23米改善的趋势。     

勃起功能障碍治疗药他达那非(tadalafil)

1 商品名 Cialis2 开发与上市厂商 本品由Lilly-lcos公司开发,2002年11月获欧盟批准,2003年2月首次在英国、瑞典、丹麦、德国及澳大利亚等多个国家上市。     

Psychosocial impact and effectiveness of tadalafil among treatment-naïve and previously-treated men with erectile dysfunction in Saudi Arabia and other Gulf-region countries

ABSTRACT

Objective: This observational, comparative study, conducted in Saudi Arabia, Kuwait, and the United Arab Emirates, assessed psychosocial and efficacy outcomes of tadalafil 20 mg on demand, over a period of 20 weeks, in men with erectile dysfunction (ED) who were treatment-naïve versus pretreated with an ED treatment other than tadalafil.

Methods: The short form of the Psychological and Interpersonal Relationship Scales (SF-PAIRS) was used to assess psychosocial outcomes (Time Concerns, Spontaneity, and Sexual Self-Confidence). Change from baseline in the International Index of Erectile Function (IIEF) erectile function (EF) domain score was used to assess effectiveness, and Global Assessment Question (GAQ) was asked to determine improvement in erections.

Results: Of 1080 patients analyzed, 557 (51.6%) were treatment-naïve and 523 (48.4%) were pretreated. In all, 500 (89.8%) treatment-naïve men and 473 (90.4%) pretreated men completed the study. Some statistically significant differences were observed in baseline characteristics between treatment-naïve and pretreated groups, including ED etiology, ED severity, duration of ED, and the presence of cormorbid cardiovascular disease, other vascular disease, and neurological disease. Adjusted mean SF-PAIRS Time Concerns domain score was significantly more improved, while the Sexual Self-Confidence domain score was significantly less improved, for the pretreated group compared with the treatment-naive group (both p < 0.0001). No significant difference was observed for the Spontaneity domain. The mean change in IIEF-ED domain score for the treatment-naïve group was 13.26 compared with 9.28 for the pretreated group (p < 0.0001). Positive responses to GAQ at the last assessment were observed in 97.3% of treatment-naïve men and 94.4% of pretreated men (p < 0.0263).

Conclusion: This large, observational study in the Gulf region demonstrates that ED patients treated with tadalafil in a naturalistic setting, report improvements in both psychosocial outcomes and erectile function, with some differences between the treatment-naïve and pretreated groups. The results of this study may assist physicians in tailoring tadalafil therapy and setting realistic treatment expectations.     

Simple and sensitive liquid chromatography–tandem mass spectrometry methods for quantification of tadalafil in rat plasma: application to pharmacokinetic study in rats

A simple and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated in rat plasma for quantification of tadalafil, a novel therapeutic agent for erectile dysfunction. Tadalafil and acebutolol (internal standard) were extracted by liquid–liquid extraction with tert-butyl methyl ether. The chromatographic separation was performed on a reverse phase C₁₈ column with a mobile phase consisting of 0.1 % formic acid and acetonitrile (45:55, v/v) at a flow rate of 0.3 mL/min. The protonated analyte was quantitated by multiple reaction monitoring with a Waters Quattro micro? API mass spectrometer. The calibration curve was linear over a concentration range of 2–2000 ng/mL, and the lower limit of quantification was 2 ng/mL with a precision (CV %) of 10.9 %. Acceptable intra-day and inter-day precision and accuracy were obtained at 3 concentration levels (3, 200, and 1500 ng/mL). Tadalafil was found to be stable in a battery of studies, including bench top, freeze–thaw, and autosampler conditions. The validated method was successfully used to determine tadalafil concentration in rat plasma samples after oral administration at a dose of 1 mg/kg.     

Screening of Indian aphrodisiac ayurvedic/herbal healthcare products for adulteration with sildenafil,tadalafil and/or vardenafil using LC/PDA and extracted ion LC–MS/TOF

Ayurvedic/herbal healthcare products are considered safe under the impression that they are derived from natural products. But recently, there have been several reports worldwide on the adulteration of synthetic PDE-5 inhibitors in aphrodisiac herbal formulations. Therefore, the objective of the present study was to explore the presence of synthetic PDE-5 inhibitors (sildenafil, tadalafil and/or vardenafil) in ayurvedic/herbal healthcare products sold in Indian market for aphrodisiac/related uses. In total, 85 herbal formulations (HFs) were included in the study. The formulations were extracted with methanol and subjected to centrifugation. The supernatant was analysed by HPLC and LC–MS/TOF. Early detection of the presence of sildenafil, tadalafil and vardenafil in the herbal samples was done by the study of extracted ion mass chromatograms at the m/z values of respective parent ions, and two prominent fragments of each. In case of sildenafil and tadalafil, adulteration was also detected by comparing the relative retention times (RR_T) and UV spectra. Further substantiation was done through comparison of accurate mass spectra with those of the two available standards. Of the 85 HFs tested, only one was eventually found to be adulterated with sildenafil. The extent of adulterant in this sample was determined to the therapeutic dose in the formulation. The study thus indicates emergence of the problem of adulteration of Indian herbal products with PDE-5 inhibitors.     

Comparison of the determination of β-lactam antibiotic drugs in plasma of rabbits by means of HPLC and of a microbiological assay

The present study compares the determination of the plasma concentrations of ampicillin, amoxycillin and cefuroxime in rabbits, by means of high performance liquid chromatography and the microbiological assay. The correlation coefficient between the data obtained by these methods are for ampicillin 0.991, amoxycillin 0.994 and cefuroxime 0.991. Plasma constituents interfering with amoxycillin in theHplc determinations, were not encountered in the plasma of man.     

Modulation of release of ATP in the major pelvic ganglion of rats

用荧光素－荧光素酶方法测定大鼠盆总神经节腺苷三磷酸（ＡＴＰ）释放．钠通道阻断剂河豚毒素（１μｍｏｌ·Ｌ－１）抑制电刺激诱发的盆总神经节ＡＴＰ的释放．灌流液中去除Ｃａ２＋并加入ＥＧＴＡ（１ｍｍｏｌ·Ｌ－１）后消除ＡＴＰ的释放．腺苷（１００μｍｏｌ·Ｌ－１），Ａ１腺苷受体激动剂环戊腺苷（０．１μｍｏｌ·Ｌ－１），毒蕈碱性受体激动剂氧化震颤素（１μｍｏｌ·Ｌ－１）和５－羟色胺（１００μｍｏｌ·Ｌ－１）减少ＡＴＰ的释放．Ａ１腺苷受体拮抗剂８－环戊基－１，３－二丙基黄嘌呤（１０ｎｍｏｌ·Ｌ－１），α２肾上腺素受体拮抗剂育亨宾（３μｍｏｌ·Ｌ－１），Ｄ２多巴胺受体拮抗剂舒必利（２０μｍｏｌ·Ｌ－１）和组胺（１００μｍｏｌ·Ｌ－１）增加ＡＴＰ的释放．结果提示，在大鼠盆总神经节存在着作为神经递质参与突触传递的ＡＴＰ释放．Ａ１腺苷受体，毒蕈碱性受体，α２肾上腺素受体，Ｄ２多巴胺受体，５－羟色胺受体及Ｈ１组胺受体激动剂或拮抗剂可以通过节前机制影响ＡＴＰ的释放     

Analysis of electronic structures of physostigmine analogs

ＡｎａｌｙｓｉｓｏｆｅｌｅｃｔｒｏｎｉｃｓｔｒｕｃｔｕｒｅｓｏｆｐｈｙｓｏｓｔｉｇｍｉｎｅａｎａｌｏｇｓＨＵＺｅｎｇＪｉａｎ，ＪＩＡＮＧＨｕａＬｉａｎｇ，ＣＨＥＮＪｉａｎＺｈｏｎｇ，ＣＨＥＮＫａｉＸｉａｎ１，ＪＩＲｕＹｕｎ（Ｓｈａｎｇｈａｉ...     

Effects of schisanhenol on antitumoractivity of adriamycin

<正> It was suggested that adriamycin (ADM) may have at least two mechanisms of tissue damage. One, which involves lipid peroxidation, is blocked by the free radical scavenger, appears to play a major role in the development of cardiomyopathy. The other, which may involve binding of ADM to DNA, appears to be the major determinant of ADM toxicity for tumor cells. So the antitumor efficiency of ADM may be dissociated from its side effect of     

(Journal of China University of Geoscien

转化及土壤重金属污染的治理等方面起重要作用,关于有机酸是否影响矿物风化的问题,自1826年Sprengel和Julien为土壤中的有机酸是否在矿物溶解中扮演重要角色展开争论以来,已经持续     

The effect of pimozide on variable-interval performance: A test of the ‘anhedonia’ hypothesis of the mode of action of neuroleptics

A quantitative behavioural test system based on Herrnstein's (1970) equation was used to test a prediction derived from the anhedonia hypothesis of neuroleptic action, that pimozide should increase the value of the behavioural parameter K _H (the reinforcement frequency needed to maintain the half-maximal response rate in variable-interval schedules). On the basis of theoretical considerations, it was shown that the equation implies that a drug which exerts such an effect on K _H must have a more profound suppressant effect on performance maintained by low reinforcement frequencies than on performance maintained by high reinforcement frequencies. Fifteen rats were trained under variable-interval 10-s and variable-interval 100-s schedules, and the effect of pimozide (0.125, 0.25, 0.33, and 0.5 mg/kg) was tested on performance maintained under each schedule. The drug suppressed performance maintained under both schedules in a dose-dependent manner, and there was no tendency for the drug to exert a greater effect on performance maintained under the lower reinforcement frequency. These results do not provide any evidence that the effect of pimozide on variable-interval performance is due to an anti-hedonic effect; rather, they are compatible with the hypothesis that pimozide impairs the capacity to respond.     

Cases analysis of rational use of medicine（45） Hypertension of Pregnancy

1.患者简介患者,女性,19岁,妊娠25周时,出现头痛,恶心,上腹部不适,血压162/108 mmHg,间隔6小时后再测血压,仍是162/108 mmHg。患者无高血压患病史。尿蛋白检查:+诊断:子痫前期(原名先兆子痫)2.用药     

Inhibitiory Effect of Scoparone on Inflammatory Mediator of Asthmatic Models of Guinea Pigs

Aim Bronchial asthma is a chronic inflammatory disease of the airways, is characterized by massive infiltration of eosinophils and airway hyperreactivity （ AHR）, which are caused by overproduction of inflammatory factors. It was reported that Scoparone possessed anti-inflammation and calcium antagonistic effects. We found that the dilatory effect of scoparone on the tracheal smooth muscle of guinea-pig, hence we presumed that scoporone might cure bronchial asthma. There has not been any report about anti-inflammation activity of scoparone on asthma, so we investigated the anti -inflammation activity of scoparone via using asthmatic models of guinea pig.     

Mode of Action: Reduction of Testosterone Availability—Molinate-Induced Inhibition of Spermatogenesis

Molinate is a preemergent herbicide that has been demonstrated to affect reproduction in the rat via alterations in sperm production. A wealth of standard toxicological studies and targeted research efforts relating to this adverse effect is available, and these were used to evaluate the utility of the Human Relevance Framework (HRF) for noncancer health effects. The hypothesized mode of action involved inhibition of the hydrolysis of cholesterol from high-density lipoprotein in the rat testes, followed by an androgen withdrawal syndrome on spermatogenesis. Some evidence is available that a similar mode of action would not be operable in humans. Despite the wealth of studies conducted in the rat, the weight of evidence is insufficient to define the mode of action for reproductive toxicity in the male rat. A principal deficiency in the database was discordance between the exposure levels observed to cause biochemical disturbances in the testes related to the hypothesized mode of action and the dose levels observed to induce the adverse outcome on spermatogenesis. For this reason, a complete MOA/human relevance analysis is not possible and, based on traditional risk assessment principles, any toxic effects are assumed to be relevant for human risk assessment.