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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • November 2015

Published In

Volume / Issue

  • 4 / 11

Start / End Page

  • 669 - 679

PubMed ID

  • 26783503

Pubmed Central ID

  • 26783503

Electronic International Standard Serial Number (EISSN)

  • 2163-8306

International Standard Serial Number (ISSN)

  • 2163-8306

Digital Object Identifier (DOI)

  • 10.1002/psp4.12017

Language

  • eng