Summary
Extended release dipyridamole (ERD) is widely used in patients after ischaemic stroke;
however, the ability of this antithrombotic agent to be stored in different blood
cells has never been explored in post-stroke patients. We hypothesised that since
ERD is known to be highly lipophilic, the drug may be present not only in plasma,
but also accumulated in platelets, leukocytes, and erythrocytes. Fifteen patients
after documented ischaemic stroke were treated with Aggrenox (ERD and lowdose aspirin
combination) BID for 30 days, and 12 of them completed the study. ERD concentrations
in blood cells and platelet-poor plasma were measured by spectrofluorimetry at Baseline,
Day 14, and Day 30 after the initiation of therapy. The background level of spectrofluorometry
readings differs slightly among the blood components (132–211 ng/ml) due to the differences
in the preparation of samples and cell isolation techniques. As expected, two weeks
of ERD therapy produced steady-state plasma concentration of dipyridamole already
at Day 14 (1,680 ±542 ng/ ml), followed by a slight not significant decrease at one
month (1,619 ±408 ng/ml). Two weeks of therapy was sufficient to achieve a consistent
dipyridamole accumulation in erythrocytes (361 ±43 ng/ml), but not in platelets (244
±78 ng/ml), or leukocytes (275 ±49 ng/ml).In fact, white blood cells continued dipyridamole
intake beyond 14 days period, and this increase (398 ± 66 ng/ml) was significant (p
= 0.02) at 30 days. Treatment with ERD in post-stroke patients resulted not only in
achievement of therapeutic plasma dipyridamole concentrations, but also deposition
of the drug in erythrocytes and leukocytes, but not in platelets. If confirmed, these
data will affect our better understanding of dipyridamole pleiotropy, and may explain
long-term benefit of ERD formulation.
Keywords
Stroke - dipyridamole - pharmacokinetics - spectrofluorimetry - platelets - erythrocytes
- leukocytes - plasma
