Format

Send to

Choose Destination
CPT Pharmacometrics Syst Pharmacol. 2014 Jul 16;3:e125. doi: 10.1038/psp.2014.22.

Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

Author information

1
1] Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden, The Netherlands [2] Netherlands Metabolomics Centre, Leiden, The Netherlands.
2
Program in Personalized and Genomic Medicine, Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
3
Duke University Medical Center, Durham, North Carolina, USA.
4
1] Duke University Medical Center, Durham, North Carolina, USA [2] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany.
5
1] Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA [2] Duke Institute for Brain Sciences, Duke University, Durham, North Carolina, USA [3] Institute of Genome Science and Policy, Duke University, Durham, North Carolina, USA.

Abstract

While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 ± 8 vs. 61 ± 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 × 10(-4), N = 12). These results suggest that serotonin is implicated in aspirin response variability.

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center