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Targeted Plasma Metabolite Profiling of Metformin in Healthy Korean Volunteers  

Lihm, Ho-Seob (Department of Family Medicine, Kosin University College of Medicine)
Cha, Jaemin (Department of Biomedical Science, Kyungpook National University Graduate School)
Seo, Jeong Ju (Department of Biomedical Science, Kyungpook National University Graduate School)
Park, Jeonghyeon (Department of Biomedical Science, Kyungpook National University Graduate School)
Lee, Joomi (Department of Biomedical Science, Kyungpook National University Graduate School)
Lee, Hae Won (Clinical Trial Center, Kyungpook National University Hospital)
Bae, Kyun Seop (Department of Clinical Pharmacology & Therapeutics, Asan Medical Center)
Kim, Woomi (Department of Pharmacology, Kosin University College of Medicine)
Yoon, Young-Ran (Department of Biomedical Science, Kyungpook National University Graduate School)
Publication Information
Journal of Korean Society for Clinical Pharmacology and Therapeutics / v.20, no.2, 2012 , pp. 175-181 More about this Journal
Abstract
Background: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to decrease the long-period complications of diabetes, including macrovascular disease. Few reports have addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose. Methods: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed. Results: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7 amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5 lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance. Conclusion: In order to explore the potential endogenous metabolites associated with the therapeutic effects of metformin, further study including non-targeted (global) metabolite profiling is needed.
Keywords
Metformin; Targeted metabolite profiling; UPLC-MS/MS;
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