Increased dipyridamole plasma concentrations associated with salicylate administration. Relationship to effects on platelet aggregation in vivo

Dipyridamole, in relatively low doses, when used in combination with aspirin was shown to be effective in normalizing reduced platelet survival seen in patients with prosthetic heart valves, whereas either drug, when tested alone, was ineffective. To determine whether this combined drug effect was due to a synergism of the two drugs or due to an alteration in the pharmacokinetics of one drug in the presence of the other, we examined the effects of aspirin and sodium salicylate on 1) the effects of dipyridamole on platelet function in vivo and 2) the concentration of dipyridamole in the plasma. Both aspirin and salicylate altered the plasma concentration of dipyridamole and prolonged the effect of dipyridamole on collagen-induced platelet aggregation in vivo in the rabbit. This effect appeared to be due to saturation of the glucuronide pathway(s) which is the major route of clearance of dipyridamole from the circulation.