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2008 Annual Meeting Abstracts
Pharmacodynamic Interaction of the Highly Uroselective α-Blocker Silodosin With the Phosphodiesterase-5 (PDE-5) Inhibitors Sildenafil and Tadalafil
Dennis N Morrison1, Gary Hoel2, Lawrence Hill2, Weining Volinn2
1Bio-Kinetic Clinical Applications, Inc., Springfield, MO;2Watson Laboratories, Salt Lake City, UT
Introduction: This placebo-controlled, open-label, crossover study was conducted to evaluate the safety and orthostatic effects of coadministration of silodosin and PDE-5 inhibitors.
Methods: Twenty-two 45- to78-year-old healthy men received 8 mg silodosin for 21 days; on days 7, 14, and 21, subjects received in random sequence a single dose of 100 mg sildenafil, 20 mg tadalafil, or placebo. Supine (baseline) and standing orthostatic measurements were performed 0 hr (predose) to 12 hr after single-dose treatment. A positive orthostatic test was defined as a decrease in systolic (or diastolic) blood pressure by >30 (or >20) mm Hg, increased heart rate (>20 bpm), or orthostatic symptoms on change of position.
Results: Mean changes from baseline in 1 min-standing orthostatic tests were similar for all treatment groups (Table). The cumulative number of positive orthostatic tests was similar for all treatments in 16 subjects <65 years (sildenafil, 52; tadalafil, 55; placebo, 49) and in 6 subjects ≥65 years (sildenafil, 12; tadalafil, 11; placebo, 9). No treatment-related adverse events of symptomatic orthostasis or dizziness were reported. No serious adverse events occurred during the study.
Conclusions: Concomitant use of silodosin and maximum doses of sildenafil or tadalafil in healthy men caused no clinically important changes in blood pressure, heart rate, or orthostatic symptoms.
Mean Changes From Baseline (CFB) in 1 Min-Standing BP/HR After Administration of PDE-5 Inhibitors | Systolic BP, CFB (mm Hg), N=22 | | | Diastolic BP, CFB (mm Hg), N=22 | | | Heart rate, CFB (bpm), N=22 | | | | Time postdose | Sil (100 mg sildenafil) | Tad (20 mg tadalafil) | Pbo (placebo) | Sil (100 mg sildenafil) | Tad (20 mg tadalafil) | Pbo (placebo) | Sil (100 mg sildenafil) | Tad (20 mg tadalafil) | Pbo (placebo) | | Predose | -2.8 | -3.0 | -5.8 | 0.0 | 0.7 | 0.4 | 13.0 | 11.2 | 12.1 | | 1 hr | -1.7 | -1.7 | -5.0 | -0.6 | 0.1 | -0.3 | 14.8 | 13.7 | 12.7 | | 2 hr | -2.0 | -5.0 | -7.2 | 0.5 | -1.9 | -2.6 | 13.8 | 13.0 | 11.9 | | 3 hr | -4.1 | -3.6 | -4.0 | 2.3 | -1.3 | 1.7 | 14.0 | 14.2 | 12.7 | | 4 hr | -4.8 | -10.2 | -5.6 | -1.6 | -5.2 | 0.0 | 15.6 | 12.7 | 13.9 | | 6 hr | -5.0 | -9.9 | -10.7 | 0.6 | -3.8 | -2.5 | 8.7 | 9.0 | 11.9 | | 8 hr | -4.1 | -3.7 | -0.7 | 1.2 | 1.4 | 3.0 | 15.4 | 13.4 | 11.5 | | 12 hr | -1.6 | -1.7 | -1.3 | 1.1 | -0.5 | 0.9 | 12.0 | 12.3 | 12.1 |
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