Time-dependent interactions of the hypotensive effects of sildenafil citrate and sublingual glyceryl trinitrate.
OBJECTIVE
To investigate the time course of the hypotensive interaction between sildenafil and glyceryl trinitrate (GTN).


METHODS
Two double-blind, placebo-controlled, randomized, crossover studies were performed. Subjects were challenged with sublingual GTN 400 microg at different times after oral sildenafil 100 mg. After each GTN challenge frequent measures of blood pressure (BP) were made. In the first study GTN was given 1-48 h after sildenafil/placebo to 33 healthy men. In the second study GTN was given 1-8 h after sildenafil/placebo to 20 men with stable angina.


RESULTS
In healthy men there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN only at 1 h. In angina patients, there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN for up to 8 h. The mean (95% confidence interval) differences in maximum systolic BP reduction (mmHg) at 1, 4, 6 and 8 h were -16 (-12, -21), -12 (-4, -20), -6 (1, -12) and -9 (-3, -15), all P < 0.05 except at 6 h (NS). At 6 and 8 h the interaction was not more than additive, and hypotensive symptoms did not occur.


CONCLUSIONS
In men with angina there is an interaction on BP reduction between sildenafil and GTN for >or= 8 h after sildenafil administration, but this is no more than additive from 6 h. These data may be helpful to clinicians who are considering the use of GTN in patients presenting with angina who have received sildenafil within 24 h.
Clinical Pharmacology Unit, The Queen's Medical Research Institute, Edinburgh, UK.
James J
JJ
Oliver
Debra M
DM
Kerr
David J
DJ
Webb
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D004812:Epidemiologic Methods; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D005996:Nitroglycerin