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Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes.

Publication ,  Journal Article
Rotroff, DM; Shahin, MH; Gurley, SB; Zhu, H; Motsinger-Reif, A; Meisner, M; Beitelshees, AL; Fiehn, O; Johnson, JA; Elbadawi-Sidhu, M; Frye, RF ...
Published in: CPT Pharmacometrics Syst Pharmacol
November 2015

Achieving hypertension (HTN) control and mitigating the adverse health effects associated with HTN continues to be a global challenge. Some individuals respond poorly to current HTN therapies, and mechanisms for response variation remain poorly understood. We used a nontargeted metabolomics approach (gas chromatography time-of-flight/mass spectrometry gas chromatography time-of-flight/mass spectrometry) measuring 489 metabolites to characterize metabolite signatures associated with treatment response to anti-HTN drugs, atenolol (ATEN), and hydrochlorothiazide (HCTZ), in white and black participants with uncomplicated HTN enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses study. Metabolite profiles were significantly different between races, and metabolite responses associated with home diastolic blood pressure (HDBP) response were identified. Metabolite pathway analyses identified gluconeogenesis, plasmalogen synthesis, and tryptophan metabolism increases in white participants treated with HCTZ (P < 0.05). Furthermore, we developed predictive models from metabolite signatures of HDBP treatment response (P < 1 × 10(-5)). As part of a quantitative systems pharmacology approach, the metabolites identified herein may serve as biomarkers for improving treatment decisions and elucidating mechanisms driving HTN treatment responses.

Duke Scholars

Published In

CPT Pharmacometrics Syst Pharmacol

DOI

ISSN

2163-8306

Publication Date

November 2015

Volume

4

Issue

11

Start / End Page

669 / 679

Location

United States

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology
  • 1116 Medical Physiology
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Rotroff, D. M., Shahin, M. H., Gurley, S. B., Zhu, H., Motsinger-Reif, A., Meisner, M., … Kaddurah-Daouk, R. (2015). Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes. CPT Pharmacometrics Syst Pharmacol, 4(11), 669–679. https://doi.org/10.1002/psp4.12017
Rotroff, D. M., M. H. Shahin, S. B. Gurley, H. Zhu, A. Motsinger-Reif, M. Meisner, A. L. Beitelshees, et al. “Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes.CPT Pharmacometrics Syst Pharmacol 4, no. 11 (November 2015): 669–79. https://doi.org/10.1002/psp4.12017.
Rotroff DM, Shahin MH, Gurley SB, Zhu H, Motsinger-Reif A, Meisner M, et al. Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes. CPT Pharmacometrics Syst Pharmacol. 2015 Nov;4(11):669–79.
Rotroff, D. M., et al. “Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes.CPT Pharmacometrics Syst Pharmacol, vol. 4, no. 11, Nov. 2015, pp. 669–79. Pubmed, doi:10.1002/psp4.12017.
Rotroff DM, Shahin MH, Gurley SB, Zhu H, Motsinger-Reif A, Meisner M, Beitelshees AL, Fiehn O, Johnson JA, Elbadawi-Sidhu M, Frye RF, Gong Y, Weng L, Cooper-DeHoff RM, Kaddurah-Daouk R. Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes. CPT Pharmacometrics Syst Pharmacol. 2015 Nov;4(11):669–679.
Journal cover image

Published In

CPT Pharmacometrics Syst Pharmacol

DOI

ISSN

2163-8306

Publication Date

November 2015

Volume

4

Issue

11

Start / End Page

669 / 679

Location

United States

Related Subject Headings

  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology
  • 1116 Medical Physiology
  • 1115 Pharmacology and Pharmaceutical Sciences