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

CPT: Pharmacometrics & Systems Pharmacology
D M RotroffR Kaddurah-Daouk

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 her...Continue Reading

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Citations

Jul 6, 2016·Frontiers in Pharmacology·Daniel M RotroffRima Kaddurah-Daouk
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Methods Mentioned

BETA
metabolomics profiling

Clinical Trials Mentioned

NCT00246519

Software Mentioned

R
miniX
SetupX

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