Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Jongno-gu, Seoul, Republic of Korea.
Clin Ther. 2012 Sep;34(9):1929-39. doi: 10.1016/j.clinthera.2012.08.002. Epub 2012 Aug 24.
Both mirodenafil, a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction, and tamsulosin, a selective α(1A)-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia, have mild vasodilational effects.
The aim of this study was to investigate the effect of mirodenafil on the hemodynamics of healthy volunteers who were administered tamsulosin.
Healthy, Korean normotensive male volunteers were enrolled in a randomized, placebo-controlled, double-blind, 2-sequence, 2-period crossover study. Mirodenafil 100 mg or placebo was administered orally after pretreatment with tamsulosin 0.2 mg once daily for 7 days in each period, with a 1-week washout period. Blood pressure (BP) and pulse rate (PR) in supine and standing positions were measured repeatedly before and until 24 hours after the administration of mirodenafil or placebo. The mean differences from the baseline values of the maximum changes of BP and PR, which were measured at 4 and 24 hours, were analyzed by using a mixed-effects model.
Eighteen subjects (mean [SD] age, 26.8 [3.9] years; weight, 65.5 [7.0] kg) were administered any trial medication, and 16 of them completed the study. For 4 hours/24 hours after mirodenafil administration, the mean maximal changes from baseline versus placebo in supine systolic BP, diastolic BP, and PR were -1.0 mm Hg (95% CI, -4.2 to 2.2) (P = 0.53)/-1.2 mm Hg (95% CI, -5.3 to 2.9) (P = 0.56), -2.1 mm Hg (95% CI, -4.6 to 0.4) (P = 0.10)/-1.1 mm Hg (95% CI, -3.9 to 1.6) (P = 0.39), and 7.2 beats/min (95% CI, 4.7 to 9.6) (P < 0.05)/4.8 beats/min (95% CI, 1.4 to 8.1) (P < 0.05), respectively. Those changes in a standing position were -4.0 mm Hg (95% CI, -8.9 to 0.9) (P = 0.10)/-4.3 mm Hg (95% CI, -10.0 to 1.5) (P = 0.13), -1.1 mm Hg (95% CI, -4.9 to 2.7) (P = 0.54)/-1.9 mm Hg (95% CI, -5.5 to 1.7) (P = 0.27), and 10.7 beats/min (95% CI, 4.4 to 16.9) (P < 0.05)/6.0 beats/min (95% CI, 0.7 to 11.3) (P < 0.05), respectively. A total of 33 adverse events (AEs) were reported in 9 of 18 subjects. The number of subjects with AEs (P = 0.13) and the number of AEs (P = 0.26) were not significantly different between the 2 groups. The most common AEs were vasodilational symptoms, such as nasal congestion, headache, and flushing.
The coadministration of mirodenafil 100 mg did not induce a significant decrease in BP when associated with an increase in PR in these healthy male Korean volunteers administered tamsulosin 0.2 mg compared with placebo. (Clinical Trial Registry, http://cris.cdc.go.kr/cris/en/: KCT0000117).
米罗地尔是一种磷酸二酯酶 5 抑制剂，用于治疗勃起功能障碍，而坦索罗辛是一种选择性α（1A）-肾上腺素能受体拮抗剂，用于治疗良性前列腺增生。两者都具有轻微的血管扩张作用。
本研究旨在探讨米罗地尔对服用坦索罗辛的健康志愿者血液动力学的影响。
健康的韩国正常血压男性志愿者被纳入一项随机、安慰剂对照、双盲、2 序列、2 期交叉研究。在每个时期中，志愿者先接受坦索罗辛 0.2mg 每日一次预处理 7 天，然后口服米罗地尔 100mg 或安慰剂，每个时期之间有 1 周的洗脱期。在口服米罗地尔或安慰剂之前和之后 24 小时内，反复测量仰卧位和站立位的血压（BP）和脉搏率（PR）。使用混合效应模型分析 4 小时和 24 小时时测量的 BP 和 PR 最大变化的从基线值的平均差异。
18 名受试者（平均[标准差]年龄，26.8[3.9]岁；体重，65.5[7.0]kg）接受了任何试验药物，其中 16 名完成了研究。与安慰剂相比，米罗地尔给药后 4 小时/24 小时，仰卧位收缩压、舒张压和 PR 的最大变化从基线值的平均差异分别为-1.0mmHg（95%CI，-4.2 至 2.2）（P=0.53）/-1.2mmHg（95%CI，-5.3 至 2.9）（P=0.56），-2.1mmHg（95%CI，-4.6 至 0.4）（P=0.10）/-1.1mmHg（95%CI，-3.9 至 1.6）（P=0.39）和 7.2 次/分（95%CI，4.7 至 9.6）（P<0.05）/4.8 次/分（95%CI，1.4 至 8.1）（P<0.05）。站立位的这些变化分别为-4.0mmHg（95%CI，-8.9 至 0.9）（P=0.10）/-4.3mmHg（95%CI，-10.0 至 1.5）（P=0.13），-1.1mmHg（95%CI，-4.9 至 2.7）（P=0.54）/-1.9mmHg（95%CI，-5.5 至 1.7）（P=0.27）和 10.7 次/分（95%CI，4.4 至 16.9）（P<0.05）/6.0 次/分（95%CI，0.7 至 11.3）（P<0.05）。在 18 名受试者中的 9 名中报告了 33 次不良事件（AE）。AE 的发生人数（P=0.13）和 AE 的发生人数（P=0.26）在两组之间无显著差异。最常见的 AE 是血管扩张症状，如鼻塞、头痛和潮红。
与安慰剂相比，在服用坦索罗辛 0.2mg 的这些健康的韩国男性志愿者中，与 PR 增加相关的米罗地尔 100mg 联合给药不会导致血压显著下降。（临床试验注册，http://cris.cdc.go.kr/cris/en/: KCT0000117）
