Pharmacometabolomic assessments of atenolol and hydrochlorothiazide treatment reveal novel drug response phenotypes

D. M. Rotroff, M. H. Shahin, S. B. Gurley, H. Zhu, A. Motsinger-Reif, M. Meisner, A. L. Beitelshees, O. Fiehn, J. A. Johnson, M. Elbadawi-Sidhu, R. F. Frye, Y. Gong, L. Weng, R. M. Cooper-Dehoff, R. Kaddurah-Daouk

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)669-679
Number of pages11
JournalCPT: Pharmacometrics and Systems Pharmacology
Volume4
Issue number11
DOIs
StatePublished - Nov 1 2015

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Hydrochlorothiazide
Atenolol
Hypertension
Metabolites
Phenotype
Drugs
Pharmaceutical Preparations
Blood Pressure
Gas Chromatography
Time-of-flight
Blood pressure
Mass Spectrometry
Gas chromatography
Therapeutics
Mass spectrometry
Plasmalogens
Signature
Metabolomics
Gluconeogenesis
Pharmacology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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 and Systems Pharmacology, 4(11), 669-679. https://doi.org/10.1002/psp4.12017

Pharmacometabolomic assessments of atenolol and hydrochlorothiazide treatment reveal novel drug response phenotypes. / Rotroff, D. M.; Shahin, M. H.; Gurley, S. B.; Zhu, H.; Motsinger-Reif, A.; Meisner, M.; Beitelshees, A. L.; Fiehn, O.; Johnson, J. A.; Elbadawi-Sidhu, M.; Frye, R. F.; Gong, Y.; Weng, L.; Cooper-Dehoff, R. M.; Kaddurah-Daouk, R.

In: CPT: Pharmacometrics and Systems Pharmacology, Vol. 4, No. 11, 01.11.2015, p. 669-679.

Research output: Contribution to journalArticle

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 2015, 'Pharmacometabolomic assessments of atenolol and hydrochlorothiazide treatment reveal novel drug response phenotypes', CPT: Pharmacometrics and Systems Pharmacology, vol. 4, no. 11, pp. 669-679. https://doi.org/10.1002/psp4.12017
Rotroff, D. M. ; Shahin, M. H. ; Gurley, S. B. ; Zhu, H. ; Motsinger-Reif, A. ; Meisner, M. ; Beitelshees, A. L. ; Fiehn, O. ; Johnson, J. A. ; Elbadawi-Sidhu, M. ; Frye, R. F. ; Gong, Y. ; Weng, L. ; Cooper-Dehoff, R. M. ; Kaddurah-Daouk, R. / Pharmacometabolomic assessments of atenolol and hydrochlorothiazide treatment reveal novel drug response phenotypes. In: CPT: Pharmacometrics and Systems Pharmacology. 2015 ; Vol. 4, No. 11. pp. 669-679.
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