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Thromb Haemost 2009; 102(03): 538-543
DOI: 10.1160/TH09-03-0158
Platelets and Blood Cells
Schattauer GmbH

Distribution of dipyridamole in blood components among post-stroke patients treated with extended release formulation

Victor Serebruany
1   HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, Maryland, USA
,
Elena Sabaeva
1   HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, Maryland, USA
,
Christopher Booze
1   HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, Maryland, USA
,
Oliver D. Atar
1   HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, Maryland, USA
,
Christian Eisert
1   HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, Maryland, USA
,
Dan Hanley
1   HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, Maryland, USA
,
for the Aggrenox® Compliance Task Force › Author Affiliations
Further Information

Publication History

Received: 10 March 2009

Accepted after major revision: 21 May 2009

Publication Date:
22 November 2017 (online)

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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
 

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