Effect of a Low Dose of Dipyridamole on Glyceryl Trinitrate Tolerance in Healthy Volunteers

Tolerance to glyceryl trinitrate (GTN) was developed in healthy volunteers by treatment with GTN patches, 10 mg/24 h. The difference (supine position-erect position) in systolic blood pressure (SBP) observed after application of GTN patches at the first day disappeared after 24-h transdermal administration for 2-4 consecutive days, indicating that tolerance to GTN had developed in the group of 12 healthy volunteers treated with active drug. Increased HR during the first day also disappeared as a sign of tolerance development to GTN. The phosphodiesterase (PDE) inhibitor dipyridamole (Dip) showed no effect on SBP in either the GTN-tolerant group or in the placebo group, and the tolerance to GTN was not reversed. The present study shows that addition of Dip to GTN cannot reverse GTN tolerance. Plasma concentrations of GTN and its two dinitrate metabolites were measured after transdermal administration. Addition of Dip to GTN showed no influence on the pharmacokinetics of the nitrates in healthy volunteers.