Time course of the interaction between tadalafil and nitrates.
OBJECTIVE
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.
Kloner
Robert A
RA
The Heart Institute, Good Samaritan Hospital, Cardiovascular Division, Keck School of Medicine, University of Southern California, Los Angeles, California 90017, USA. rkloner@goodsam.org
Hutter
Adolph M
AM
Emmick
Jeffrey T
JT
Mitchell
Malcolm I
MI
Denne
Jonathan
J
Jackson
Graham
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000188:drug therapy; D002243:Carbolines / Q000627:therapeutic use*; D000075202:Contraindications; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D000068581:Tadalafil; D013997:Time Factors
D002243:Carbolines; D009566:Nitrates; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil