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Abstract
While phosphodiesterase type 5 inhibitors have been used for erectile dysfunction with acceptable safety profile, they can induce orthostatic hypotension in patients taking antihypertensive drugs with blood pressure lowering effect. This study evaluated the hemodynamic effects of 100 mg mirodenafil in hypertensive patients taking an amlodipine. Thirteen hypertensive patients who were taking 5 or 10 mg of amlodipine once daily participated in a randomized, double-blind, placebo-controlled, crossover study. A single oral dose of mirodenafil 100 mg or placebo was administered at 4.5 hour after administration of amlodipine. The maximal change in systolic and diastolic blood pressure (∆maxSBP and ∆maxDBP) and pulse rate (∆maxPR) were compared between mirodenafil and placebo periods. Twelve patients completed this study and were included analysis. The values of ∆maxPR in standing and supine position were significantly greater in the mirodenafil period (13.25±7.12 and 11.17±4.86 beats/minute) when compared to the placebo (8.50±4.72 and 6.58± 3.90 beats/minute). The ∆maxSBP and ∆maxDBP in standing position appeared to be lower in the mirodenafil period, but they were not statistically different from those in the placebo period (∆maxSBP = −7.42±5.6 vs −4.42±5.37 mmHg and ∆maxDBP = −7.17±5.72 vs −3.50±3.37 mmHg). Both ∆maxSBP and ∆maxDBP in standing and supine position were not significantly different between mirodenafil and placebo. This study demonstrated that mirodenafil exerted minimal hemodynamic effects in the patients taking amlodipine, that is unlikely associated with a clinically significant hypotensive event
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Figure 1.
Effects of mirodenafil on hemodynamic variables while standing. Mean systolic (a) and diastolic (b) blood pressure, and pulse rate (c) following administration of amlodipine. Mirodenafil or placebo was administered at 4.5 h. All data are reported±standard deviations.
Figure 2.
Effects of mirodenafil on hemodynamic variables while supine. Mean systolic (a) and diastolic (b) blood pressure, and pulse rate (c) following administration of amlodipine. Mirodenafil or placebo was administered at 4.5 h. All data are reported±standard deviations.
Table 1.
Baseline and effects of mirodenafil or placebo on hemodynamic variables in stable hypertensive patients taking amlodipine (n=12)
| Amlodipine + mirodenafil∗ | Amlodipine + placebo∗ | Mean difference† | p-value‡ | ||
|---|---|---|---|---|---|
| Standing | Baseline SBP | 121.1 (8.7) | 122.2 (5.3) | 0.594 | |
| Baseline DBP | 81.4 (8.0) | 81.5 (5.9) | 0.664 | ||
| Baseline PR | 74.0 (11.5) | 72.8 (10.0) | 0.400 | ||
| ∆maxSBP | –7.42 (5.60) | –4.42 (5.37) | –2.51 (−6.24∼1.22) | 0.164 | |
| ∆maxDBP | –7.17 (5.72) | –3.50 (3.37) | –3.31 (−7.17∼0.54) | 0.084 | |
| ∆maxPR | 13.25 (7.12) | 8.50 (4.72) | 5.16 (1.09∼9.22) | 0.018 | |
| Supine | Baseline SBP | 119.2 (9.9) | 119.1 (9.2) | 0.860 | |
| Baseline DBP | 74.5 (7.0) | 75.4 (7.2) | 0.824 | ||
| Baseline PR | 64.4 (7.7) | 63.7 (7.0) | 0.365 | ||
| ∆maxSBP | –6.25 (5.05) | –4.33 (7.23) | –1.33 (−6.44∼3.78) | 0.575 | |
| ∆maxDBP | –7.00 (4.67) | –5.25 (4.71) | –1.50 (−4.28∼1.28) | 0.257 | |
| ∆maxPR | 11.17 (4.86) | 6.58 (3.90) | 4.39 (1.11∼7.66) | 0.014 |
Table 2.
Calculated AUEC values of the hemodynamic variables after mirodenafil or placebo treatment in stable hypertensive patients (n=12)
| Amlodipine + Mirodenafil∗ | Amlodipine + Placebo∗ | Mean Difference† | p-value‡ | ||
|---|---|---|---|---|---|
| Standing | AUEC0∼8h, SBP | –19.65 (18.40) | –10.52 (14.45) | –7.64 (−18.81∼3.54) | 0.159 |
| AUEC0∼8h, DBP | –19.54 (18.86) | –7.44 (7.62) | –10.55 (−21.47∼0.37) | 0.057 | |
| AUEC0∼8h, PR | 56.42 (36.25) | 26.67 (19.07) | 32.28 (8.28∼54.28) | 0.013 | |
| Supine | AUEC0∼8h, SBP | –18.56 (18.42) | –13.19 (28.38) | –3.43 (−18.85∼11.99) | 0.631 |
| AUEC0∼8h, DBP | –22.25 (21.64) | –15.02 (18.31) | –6.11 (−14.77∼2.55) | 0.147 | |
| AUEC0∼8h, PR | 44.50 (21.40) | 18.73 (13.70) | 25.23 (11.75∼38.70) | 0.002 |
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