液相色谱-质谱联用同时测定西洋参制剂中人参皂苷Rg1、Re、Rb1及抗疲劳类非法添加含量

目的 建立同时测定西洋参制剂中人参皂苷Rg1、Re、Rb1及抗疲劳类非法添加含量的液相色谱-质谱联用方法.方法采用Agilent ZORBAX SB-C18色谱柱（3.0mm×150mm,3.5μm）,流动相A为含0.1%乙酸的20mmol·L-1乙酸铵溶液,流动相B为甲醇∶乙腈（3：2）的混合溶液,采用线性梯度洗脱;流速为200μL·min-1,柱温35℃.质谱条件采用电喷雾离子化（ESI）方式,正负离子模式,以多级反应监控（MRM）模式对西地那非、伐地那非、他达拉非、人参皂苷Rg1、Re和Rb1进行含量测定.结果 西地那非、伐地那非、他达拉非、人参皂苷Rg1、Re和Rb1分别在2.99～59.85,0.43～8.60,3.32～66.42,3.16～63.29,2.63～52.68,4.15～82.93μg·mL-1浓度范围内与峰面积呈良好线性关系.西洋参制剂中西地那非、伐地那非、他达拉非、人参皂苷Rg1、Re和Rb1的平均加样回收率均介于92.9%～103.3%之间.结论 本法简单、快速、灵敏、准确,可用于西洋参制剂中西地那非、伐地那非、他达拉非、人参皂苷Rg1、人参皂苷Re和Rb1含量测定,为该药的质量控制提供依据.     

Vardenafil: a new oral treatment for erectile dysfunction

Vardenafil is a new phosphodiesterase type-5 inhibitor for the treatment of men with erectile dysfunction (ED). It was licensed in Europe in spring 2003 and in the USA in late 2003. It is a potent and selective inhibitor of the enzyme phosphodiesterase type 5, and in the presence of an erectile stimulus potentiates the intracellular actions of cyclic guanylate monophosphate. Several large, placebo-controlled trials have demonstrated efficacy both in the broad population of men with ED and in men with more difficult to treat ED. It is well tolerated with a side effect profile typical of this class of drugs. It has a rapid onset of action and has demonstrable efficacy for men using the medication for up to 2 years.     

长期口服小剂量伐地那非治疗按需服药无效ED的疗效观察

目的:评估持续口服小剂量伐地那非治疗按需服药无效的勃起功能障碍(ED)患者的疗效及停药后效果维持状况.方法:将按需服药无效的39例ED患者改用长期口服小剂量伐地那非治疗3个月,在治疗前后及停药后3个月分别记录患者国际勃起功能指数-5(International index of erectile function-5,IIEF-5)评分及患者性生活日记中插入和保持勃起的成功率,并且记录治疗前后夫妻性满意度.结果:本组患者治疗后主要疗效指标均高于治疗前,且治疗前后指标差异有统计学意义(P<0.01);停药后3个月,主要指标仍高于基线水平,且差异有统计学意义(P<0.05).结论:每天口服小剂量伐地那非对约半数(48.6%)按需服药无效的ED患者,可改善勃起功能,且安全、有效.     

Platelet Cyclic Guanosine Monophosphate as a Biomarker of Phosphodiesterase Type 5 Inhibitor Efficacy in the Treatment of Erectile Dysfunction: A Randomized Placebo-Controlled Study

Background

Phosphodiesterase 5 inhibitors (PDE5-Is) are a mainstay in the therapy of erectile dysfunction (ED). The primary end point of clinical efficacy, both in clinical studies and normal practice, is represented by the International Index of Erectile Function (IIEF).

Objective

To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED.

Design, setting, and participants

The study enrolled 46 patients with psychogenic, organic, and mixed ED (20–71 yr of age; IIEF score <26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo.

Intervention

All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment.

Measurements

Platelet cGMP was measured in both placebo and vardenafil groups. All the patients completed the IIEF-Erectile Function (EF) domain and the sexual encounter profile (SEP) and underwent visual sexual stimulation (VSS) coupled with Rigiscan. All the measurements were performed prior to starting the protocol and after the 6 wk of treatment.

Results and limitations

Platelet cGMP production was significantly (p < 0.05) elevated in patients taking 5 mg vardenafil versus placebo. Vardenafil was not superior to placebo in improving IIEF-EF and SEP scores. Conversely, VSS-Rigiscan revealed a significant amelioration (p < 0.028) in the vardenafil group versus placebo. The changes in platelet cGMP level correlated well with VSS-Rigiscan (p = 0.0037) but not with IIEF-EF and SEP.

Conclusions

Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Larger clinical studies are needed to further validate the use, utility, and limits of this assay.     

A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

INTRODUCTION: Benign prostatic hyperplasia (BPH) is associated with bothersome lower urinary tract symptoms (LUTS) and reduced patient quality of life (QoL). Phosphodiesterase (type) 5 (PDE5) inhibitors such as vardenafil are commonly used for the treatment of erectile dysfunction (ED), but have also been shown to improve the symptoms of BPH. This randomised, double-blind, placebo-controlled study investigated the effects of vardenafil on LUTS and QoL in men with BPH/LUTS, with or without concomitant ED. METHODS: Men aged 45-64 yr with BPH/LUTS and an International Prostate Symptom Score (IPSS) > or =12 were randomised to receive either 10mg vardenafil or placebo twice daily. LUTS were assessed with the use of two primary efficacy parameters, IPSS score and maximum urinary flow rate (Qmax), as well as postvoid residual (PVR) urine volume; ED was measured with the use of the erectile function (EF) domain score of the International Index of Erectile Function (IIEF-EF); and QoL was assessed with the Urolifetrade mark QoL-9 questionnaire. RESULTS: After 8 wk of treatment, there was a significant improvement in the IPSS total score in the vardenafil group compared with placebo (-5.9 and -3.6, respectively; p=0.0013). Nominally significant improvements in irritative and obstructive IPSS subscores (p=0.0017 and p=0.0081, respectively), EF (p=0.0001), and Urolife QoL-9 (p<0.0001) were also associated with vardenafil treatment. Qmax and PVR urine volume did not change significantly with treatment, although baseline values were already considered close to normal. Vardenafil was generally well tolerated, with most adverse events considered mild or moderate in severity. CONCLUSIONS: Vardenafil treatment significantly improved LUTS, EF, and QoL in men with BPH/LUTS. Vardenafil may be considered a promising treatment option for men with symptoms secondary to BPH.     

伐地那非治疗高血压患者勃起功能障碍的有效性和安全性

勃起功能障碍(erectile dysfunction,ED)在高血压患者中的发病率明显高于非高血压人群,由于担心联合用药会出现严重不良反应,医生往往不愿为该类患者处方治疗ED的药物。伐地那非是一种新型高选择性磷酸二酯酶5型抑制剂,它对心血管系统的安全性已被多项临床试验所证实。最近进行的一项大型临床研究表明,对于同时服用多种降压药的高血压合并ED患者,伐地那非能够显著改善患者的勃起功能,并且使用安全,尤其对于血压或心率等项指标均未见临床意义的改变。     

金蚧片联合伐地那非治疗勃起功能障碍的疗效观察

目的探讨金蚧片联合伐地那非治疗勃起功能障碍的临床疗效。方法选取2018年11月—2020年11月在天津市泰达医院泌尿外科门诊治疗的96例勃起功能障碍患者,根据随机数字表法分为对照组和治疗组,每组各48例。对照组口服盐酸伐地那非片,10 mg/次,在性交前25～60 min服用。治疗组在对照组的基础上口服金蚧片,4片/次,3次/d。两组连续服用药物8周。观察两组的临床疗效,比较两组治疗前后阴茎血流动力学指标、国际勃起功能评分-5(IIEF-5)、勃起硬度评分(EHS)、睾酮水平变化情况。结果治疗后,治疗组总有效率是97.92%,显著高于对照组的81.25%(P0.05)。治疗后,治疗组患者阴茎血流动力学中舒张末期峰值流速(EDV)、血流阻力指数(RI)均高于对照组,但收缩期峰值流速(PSV)低于对照组(P0.05);且治疗后,治疗组患者阴茎血流动力学中各指标改善优于对照组(P0.05)。治疗后,两组患者IIEF-5、EHS评分均显著升高;治疗后,治疗组IIEF-5、EHS评分均显著高于对照组(P0.05)。治疗后,两组患者睾酮水平显著升高(P0.05),且治疗后治疗组睾酮水平高于对照组(P0.05)。结论金蚧片联合伐地那非治疗勃起功能障碍疗效显著,可有效改善阴茎勃起功能,且具有较高的治疗安全性,值得临床借鉴与推广。     

伐地那非治疗勃起功能障碍的多中心、随机、双盲、对照研究

目的　观察伐地那非治疗勃起功能障碍的安全性和有效性。　方法　采用多中心、随机、双盲、安慰剂对照的方法 ,在国内 7家中心对 6 2 4例勃起功能障碍者口服伐地那非的勃起功能改善情况进行临床观察。患者随机按 1∶1∶1∶1进入安慰剂组及伐地那非 5、10、2 0mg组 ,每组各 15 6例 ,完成 4周洗脱期和 12周治疗期。患者按需在性交前 1h服用 1片研究药物。每日最多服用 1次研究药物。观察治疗 12周后国际勃起功能指数 (IIEF)问卷中有关勃起功能部分 (问题 1～ 5和 15 )的得分 ,患者日记中有关插入的成功率及成功保持勃起的成功率。　结果　共有 6 0 2例 (96 .5 % )进入安全性评估和意向性分析 ,各组分别为安慰剂组 14 8例 (94 .9% )、5mg组 15 1例 (96 .8% )、10mg组 15 0例 (96 .2 % )、2 0mg组 15 3例 (98.1% )。完全符合方案人群共 4 6 8例 (75 .0 % ) ,各组分别为 :安慰剂组 12 0例 (76 .9% )、5mg组 118例 (75 .6 % )、10mg组 10 6例 (6 8.0 % )、2 0mg组 12 4例 (79.5 % )。意向性分析人群的IIEF勃起功能部分 (问题 1～ 5 ,15 )得分的统计结果 ,用药 12周后 ,伐地那非 5mg组、10mg组和 2 0mg组的平均得分基线分别为 13.3分、14 .1分和 13.6分 ,分别增加到 2 2 .2分、2 2 .8分和 2 3.6分 ,与安慰剂组     

Prescribing all phosphodiesterase 5 inhibitors to a patient with erectile dysfunction--a realistic and feasible option in everyday clinical practice--outcomes of a simple treatment regime

Objective

In clinical practice, to apply and evaluate outcomes of a treatment regime, in which the patient had the opportunity to try all the available phosphodiesterase 5 (PDE5) inhibitors.

Methods

Patients eligible for treatment with PDE5 inhibitors were prescribed 8 tablets with a shorter-acting substance (four tablets sildenafil 100 mg and four tablets vardenafil 20 mg) and eight tablets with a long-acting substance (tadalafil 20 mg). Outcomes of the regime were recorded.

Results

Of the 186 patients, 64 (34%) had not been treated previously (naïve), and 122 (66%) were undergoing treatment for their erectile dysfunction. The overall treatment response was 89% (165 of 186 patients); 78% (n = 145 of 186 patients) tested all three substances. No significant difference in choice between long- and shorter-acting medications in the overall material was observed. Two thirds of the naïve patients (n = 64) preferred a shorter-acting substance (p < 0.01). Every fifth man requested both a shorter- and a long-acting medication to accommodate his need.

Conclusion

If patients are given the opportunity in clinical practice to try all three available PDE5 inhibitors, the overall response rate is very high, almost 90%. No significant difference in patient preference between long- and shorter-acting drugs was observed. Treatment choice was based mainly on efficacy or duration of effect.     

Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific type V phosphodiesterase inhibitor

AIM: To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage.METHODS: Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin.Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively.RESULTS: There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 ± 3.49,and mean ulcer area; 21.00 ± 12.35). Ulcer counts were diminished with famotidine 5 mg/kg (4.12 ± 2.47, P > 0.05), 20 mg/kg (2.37 ± 4.43, P < 0.05), vardenafil 2 mg/kg (4.37 ± 3.06), and vardenafil 10 mg/kg (1.25 ± 1.38, P < 0.05) compared to the indomethacin group.Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 ± 2.97, P < 0.001), famotidine 20 mg/kg (0.94 ± 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 ± 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 ± 0.88, P < 0.001) compared to the indomethacin group. MDA levels were significantly higher in indomethacin group (28.48 ± 14.51), compared to the famotidine 5 mg/kg (6,21 ± 1.88, P < 0.05), famotidine 20 mg/kg (5.88 ± 1.60. P < 0.05), vardenafil 2 mg/kg (15.87 ± 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 ± 4.50,P < 0.05). NO concentration in gastric tissues of the famotidine groups were significantly increased ( P < 0.05),but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed diminished gastric damage for pretreatment groups compared to the indomethacin group ( P < 0.05).CONCLUSION: Vardenafil affords a significant dosedependent protection against indomethacin induced gastric mucosal lesions in rats.