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Effects of Continuous Albuterol Inhalation on Serum Metabolome in Healthy Subjects: More Than Just Lactic Acid
Author(s) -
Nowadly Craig D.,
Liao ShuYi,
Rose John S.
Publication year - 2021
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1781
Subject(s) - lactic acid , metabolome , lactic acidosis , gluconeogenesis , pyruvic acid , glycolysis , metabolism , metabolomics , chemistry , fatty acid , medicine , acidosis , anaerobic exercise , endocrinology , biochemistry , pharmacology , biology , physiology , chromatography , genetics , bacteria
Treatment with β2‐agonists may cause elevated lactic acid, the end product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with β2‐agonists is caused by changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown, and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study was to investigate the impact of 1 hour of continuous albuterol on the untargeted serum metabolome of healthy subjects. Twenty‐four healthy participants received 7.5 mg of continuous albuterol for 1 hour. Baseline, 1‐hour, and 2‐hour lactic acid levels were drawn. Samples obtained at baseline and 1 hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour ( P = .02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, P = .02), although there was overlap in lactate levels across times. For metabolomic analysis, fatty acids, organic acids, and sugars were elevated, and amino acids were reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after false discovery rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data support recent hypotheses that β2‐receptor activation stimulates lactic acid production, altering aerobic glycolysis, gluconeogenesis, and free fatty acid production.