Dipyridamole: pharmacokinetics and effects on aspects of platelet function in man.

Abstract

1. The effect of dipyridamole on platelet function was measured in twelve normal subjects given 150 or 200 mg tablets as single and multiple doses, and in six subjects given single doses of 25, 50 and 100 mg and multiple doses of 50 mg 8 hourly. 2. Platelet aggregation was measured in response to ADP and collagen. In the subjects given 150/200 mg, the platelets were assayed for content of cyclic AMP and for formation of thromboxane after addition of collagen. The responses to ADP and collagen and the cyclic AMP content were assessed in both the presence and absence of added PGE1. The pharmacokinetics of dipyridamole were studied in all subjects. 3. One hour after 150/200 mg single doses of dipyridamole there was significant inhibition of platelet aggregation in response to both collagen and ADP. There was no detectable effect on aggregation at other time points or with lower doses of dipyridamole. The addition of PGE1 to platelets prior to testing did not enhance the effect of dipyridamole on platelet aggregation. 4. In multiple doses, dipyridamole (150/200 mg twice daily for 11 days) had no detectable effect on platelet aggregation. 5. Dipyridamole did not have any effect on platelet cyclic AMP content, whether or not PGE1 was added prior to assay. 6. Dipyridamole did not affect platelet thromboxane formation. 7. Plasma dipyridamole concentrations were maximal 1‐2 h after ingestion, at the same time that inhibition of platelet aggregation was detected. The concentrations declined in a biexponential fashion, with a terminal half life of 24.1 +/‐ 1.9 h (mean +/‐ s.e. mean). In six of the 17 subjects, the mean steady state plasma concentration was less than 75% of the value predicted from the single dose data.

Effects of Dipyridamole Coadministration on the Pharmacokinetics of Ribavirin in Healthy Volunteers

“…It has been reported that for DP to produce inhibitory effects on erythrocyte uptake of RBV in vitro, a DP concentration of 25 µM was required, 27) which is an extremely higher concentration than that of circulating DP (0.74 µM) under repeated administration of 25 mg DP. 28) Since the percentage of unbound DP in plasma was 0.88%, 29) the DP concentration that directly contacts erythrocyte SLC29A1 is estimated to be lower still (0.0065 µM). These speculations may explain why the erythrocyte disposition of RBV was not altered by coadministration of DP.…”

Platelet function inhibitors and platelet function testing in neurointerventional procedures

“…Following oral administration of dipyridamole, the time to peak plasma concentration is 1–2 h (mean 75 min),75 with a complex metabolic breakdown yielding a half-life of 10–13 h,76 with some reports up to 24 h 75. Given its poor bioavailability, an extended release form is typically prescribed and, in terms of stroke prevention, it has been formulated with aspirin as Aggrenox (25 mg aspirin + 200 mg dipyridamole) given twice daily, as determined by the European Stroke Prevention Study 77 78.…”

Anti-platelet agents in pediatric cardiac practice

“…[4] Dipyridamole is eliminated by hepatic biotransformation to monoglucuronide, which almost exclusively is subjected to biliary and faecal excretion. [5]…”