Time-dependent interactions of the hypotensive effects of sildenafil citrate and sublingual glyceryl trinitrate

Br J Clin Pharmacol. 2009 Apr;67(4):403-12. doi: 10.1111/j.1365-2125.2009.03375.x.

Abstract

Aim: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Pressure / drug effects*
  • Drug Interactions
  • Epidemiologic Methods
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Nitroglycerin / administration & dosage
  • Nitroglycerin / pharmacology*
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / pharmacology*
  • Piperazines / administration & dosage
  • Piperazines / pharmacology*
  • Purines / administration & dosage
  • Purines / pharmacology
  • Sildenafil Citrate
  • Sulfones / administration & dosage
  • Sulfones / pharmacology*
  • Time Factors
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology*

Substances

  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate
  • Nitroglycerin