Targeted Plasma Metabolite Profiling of Metformin in Healthy Korean Volunteers.
10.12793/jkscpt.2012.20.2.175
- Author:
Ho Seob LIHM
1
;
Jaemin CHA
;
Jeong Ju SEO
;
Jeonghyeon PARK
;
Joomi LEE
;
Hae Won LEE
;
Kyun Seop BAE
;
Woomi KIM
;
Young Ran YOON
Author Information
1. Department of Family Medicine, Kosin University College of Medicine, Busan, Korea.
- Publication Type:Original Article
- Keywords:
Metformin;
Targeted metabolite profiling;
UPLC-MS/MS
- MeSH:
Alanine;
Amino Acids;
Blood Glucose;
Blood Urea Nitrogen;
Chromatography, Liquid;
Creatinine;
Diabetes Mellitus, Type 2;
Glutamic Acid;
Humans;
Lactic Acid;
Leucine;
Lysine;
Lysophosphatidylcholines;
Male;
Metformin;
Phenylalanine;
Plasma;
Tandem Mass Spectrometry;
Tryptophan;
Valine
- From:Journal of Korean Society for Clinical Pharmacology and Therapeutics
2012;20(2):175-181
- CountryRepublic of Korea
- Language:Korean
-
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.
