Clinical pharmacokinetics of dipyridamole.

The pharmacokinetics off dipyridamole were studied in six normal subjects and 20 patients. The normal subjects received 20 mg IV each and five also took a 50 mg oral dose. Concentrations after the intravenous dose showed a tri-exponential decline with a terminal half-life of 11.6 +/- 2.2 hr (mean +/- S.D.). Total plasma clearance was 138 +/- 30 ml/min and the apparent volume of distribution was 141 +/- 51 l. Peak concentrations after oral dipyridamole occurred 2--2.5 hr after the dose. Systemic availability of the oral dose was 52 +/- 23%. Plasma protein binding was 99.13 +/- 0.24%. Twenty patients, admitted for coronary artery bypass grafting, received total daily doses of 150 mg, either as 50 mg tid or 75 mg bid. Based on drug cumulation during chronic dosing, the terminal half-life averaged about half a day. There was wide interpatient variability, averaging about 10-fold, in observed plasma concentrations for both dosage regimens. The bid regimen was not associated with lower trough concentrations of the drug than the tid regimen. These results indicate that dipyridamole concentrations vary widely in patients receiving the drug, and suggest that it could be administered twice a day, and that dipyridamole levels should be monitored for the antithrombotic effect in clinical studies.