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Medline ® Abstract for Reference 76

of 'Treatment of male sexual dysfunction'

76
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Time course of the interaction between tadalafil and nitrates.
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Kloner RA, Hutter AM, Emmick JT, Mitchell MI, Denne J, Jackson G
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J Am Coll Cardiol. 2003;42(10):1855.
 
OBJECTIVES: This study was designed to determine the time course of nitrate interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half-life (t(1/2)) of 17.5 h.
BACKGROUND: The PDE5 inhibitors augment the blood pressure (BP)-lowering effects of nitrates, yet the time course of this interaction is unclear. Recent guidelines from the American College of Cardiology/American Heart Association recommend that nitrates be withheld for 24 h after taking sildenafil (t(1/2) = 4 h).
METHODS: Male subjects (n = 150) received seven consecutive daily doses of placebo or tadalafil (20 mg). On day 7 and beyond, subjects received repeated doses of sublingual nitroglycerin (0.4 mg) after the last dose of placebo or tadalafil. After a 10- to 21-day washout period, subjects crossed over to either placebo or tadalafil, and nitrate dosing was repeated.
RESULTS: In response to nitroglycerin at 4, 8, and 24 h, standing systolic BP fell below 85 mm Hg in more subjects on tadalafil compared with placebo (p<0.05), with no difference in the response to nitroglycerin at 48, 72, and 96 h (p>0.2). Similar observations were made for standing diastolic BP<45 mm Hg, decrease in systolic BP>30 mm Hg, and decrease in diastolic BP>20 mm Hg. Nitroglycerin also evoked greater mean maximal decreases in standing systolic BP at 8 and 24 h after taking tadalafil versus placebo (p<0.02), with no significant difference at 48, 72, or 96 h (p>0.49).
CONCLUSIONS: The hemodynamic interaction between tadalafil and sublingual nitroglycerin lasted 24 h, but was not seen at 48 h and beyond. Similar to other PDE5 inhibitors, tadalafil should not be administered in combination with organic nitrates.
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The Heart Institute, Good Samaritan Hospital, Cardiovascular Division, Keck School of Medicine, University of Southern California, Los Angeles, California 90017, USA. rkloner@goodsam.org
PMID