Drug Information for DIPYRIDAMOLE TABLETS, USP (Barr Laboratories, Inc.): Clinical Pharmacology

  • It is believed that platelet reactivity and interaction with prosthetic cardiac valve surfaces, resulting in abnormally shortened platelet survival time, is a significant factor in thromboembolic complications occurring in connection with prosthetic heart valve replacement.

    Dipyridamole has been found to lengthen abnormally shortened platelet survival time in a dose-dependent manner.

    In three randomized controlled clinical trials involving 854 patients who had undergone surgical placement of a prosthetic heart valve, dipyridamole, in combination with warfarin, decreased the incidence of postoperative thromboembolic events by 62 to 91% compared to warfarin treatment alone. The incidence of thromboembolic events in patients receiving the combination of dipyridamole and warfarin ranged from 1.2 to 1.8%. In three additional studies involving 392 patients taking dipyridamole and coumarin-like anticoagulants, the incidence of thromboembolic events ranged from 2.3 to 6.9%.

    In these trials, the coumarin anticoagulant was begun between 24 hours and 4 days postoperatively, and the dipyridamole was begun between 24 hours and 10 days postoperatively. The length of follow-up in these trials varied from 1 to 2 years.

    Dipyridamole does not influence prothrombin time or activity measurements when administered with warfarin.

  • Mechanism of Action:

  • Dipyridamole is a platelet adhesion inhibitor, although the mechanism of action has not been fully elucidated. The mechanism may relate to inhibition of red blood cell uptake of adenosine, itself an inhibitor of platelet reactivity, phosphodiesterase inhibition leading to increased cyclic-3', 5'-adenosine monophosphate within platelets, and inhibition of thromboxane A2 formation which is a potent stimulator of platelet activation.

  • Hemodynamics:

  • In dogs intraduodenal doses of dipyridamole of 0.5 to 4.0 mg/kg produced dose-related decreases in systemic and coronary vascular resistance leading to decreases in systemic blood pressure and increases in coronary blood flow. Onset of action was in about 24 minutes and effects persisted for about 3 hours.

    Similar effects were observed following IV dipyridamole in doses ranging from 0.025 to 2.0 mg/kg.

    In man the same qualitative hemodynamic effects have been observed. However, acute intravenous administration of dipyridamole may worsen regional myocardial perfusion distal to partial occlusion of coronary arteries.

  • Pharmacokinetics and Metabolism:

  • Following an oral dose of dipyridamole, the average time to peak concentration is about 75 minutes. The decline in plasma concentration following a dose of dipyridamole fits a two-compartment model. The alpha half-life (the initial decline following peak concentration) is approximately 40 minutes. The beta half-life (the terminal decline in plasma concentration) is approximately 10 hours. Dipyridamole is highly bound to plasma proteins. It is metabolized in the liver where it is conjugated as a glucuronide and excreted with the bile.

  • Drug Information Provided by National Library of Medicine (NLM).