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

Journal:Thrombosis and Haemostasis
ISSN:0340-6245
DOI:http://dx.doi.org/10.1160/TH09-03-0158
Issue:2009: 102/3 (Sep) pp. 421-610
Pages:538-543

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

Victor Serebruany; Elena Sabaeva; Christopher Booze; Oliver D. Atar; Christian Eisert; Dan Hanley; for the Aggrenox® Compliance Task Force

HeartDrug™ Research Laboratories, Johns Hopkins University, Baltimore, Maryland, USA

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 low-dose 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

Pharmacokinetics, leukocytes, Stroke, plasma, Platelets, dipyridamole, erythrocytes, spectrofluorimetry

DOI

http://dx.doi.org/10.1160/TH09-03-0158

You may also be interested in...

1.

Victor L. Serebruany1,2, Alex I. Malinin1, Dan F. Hanley2

Thrombosis and Haemostasis 2008 99 1: 116-120

http://dx.doi.org/10.1160/TH07-09-0563

2.

Henri Wallaschofski 1, Tobias Lohmann 2, Eva Hild 3, Anna Kobsar 3, Annelie Siegemund 4, E. Spilcke-Liss 1, Betina Hentschel 5, Christian Stumpf 6, Werner G. Daniel 6, Christian D. Garlichs 6, Martin Eigenthaler 3

Thrombosis and Haemostasis 2006 96 1: 38-44

http://dx.doi.org/10.1160/TH05-09-0634

3.

I. Gosk-Bierska (1, 2), R. D. McBane (1), Y. Wu (1), J. Mruk (3, 4), A. Tafur (1), T. McLeod (1), W. E. Wysokinski (1)

Thrombosis and Haemostasis 2011 106 1: 75-82

http://dx.doi.org/10.1160/TH10-11-0765



Articles

You've 611 Article(s) in your Basket.

TH 107.5

Clinical Focus on GPIIb/IIIa inhibitors: In the May issue of Thrombosis and Haemostasis Armstrong...

TH 107.4

The April 2012 issue of Thrombosis and Haemostasis TH 107.4 is a Theme Issue by A. Schober, T....

Thrombosis and Haemostasis official organ of Spanish Society for Thrombosis and Haemostasis

Thrombosis and Haemostasis, founded in 1957, has become the official organ of the Spanish Society...