Targeted Plasma Metabolite Profiling of Metformin in Healthy Korean Volunteers

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.

Targeted Plasma Metabolite Profiling of Metformin in Healthy Korean Volunteers

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.

Results of 2012 KoNECT Certification Program of the Human Resource Project

BACKGROUND: In recent years, clinical trials have considerably increased and relevant education programs to clinical trials have been developed and implemented since 2008 in Korea. To enhance the quality as well as global competitiveness of clinical trial professionals (CTPs), a certification program of the human resource is needed. Accordingly, in Korea the first and the second certification examinations were implemented in February and October 2012, respectively. In this paper, introduction of the certification program of the human resource is described, and results of the certification examinations and questionnaire survey are presented. METHODS: Data including the examination results and questionnaire survey was collected by cooperative officials in Korea National Enterprise for Clinical Trials. Applicants who were selected eligible for examination by the steering committee were asked to complete questionnaires provided with the test papers on the day of the certification examination. RESULTS: In the first certification examination, a total of 221 eligible participants completed the examination. 99.5 % of the participants responded the questionnaire survey. In the second examination, a total of 223 applicants participated. The examination consisted of 50 multiple-choice questions with cut-off score of 70 per cent score.176 & 194 CTPs passed the first & second examinations respectively. CONCLUSION: This paper that described the results of the two certification tests and questionnaire surveys might be helpful in establishment and activation of the certification program in the future. Quality improvement of CTPs and international competitiveness of clinical trial in Korea can be anticipated by the certification program.

Results of 2012 KoNECT Certification Program of the Human Resource Project

BACKGROUND: In recent years, clinical trials have considerably increased and relevant education programs to clinical trials have been developed and implemented since 2008 in Korea. To enhance the quality as well as global competitiveness of clinical trial professionals (CTPs), a certification program of the human resource is needed. Accordingly, in Korea the first and the second certification examinations were implemented in February and October 2012, respectively. In this paper, introduction of the certification program of the human resource is described, and results of the certification examinations and questionnaire survey are presented. METHODS: Data including the examination results and questionnaire survey was collected by cooperative officials in Korea National Enterprise for Clinical Trials. Applicants who were selected eligible for examination by the steering committee were asked to complete questionnaires provided with the test papers on the day of the certification examination. RESULTS: In the first certification examination, a total of 221 eligible participants completed the examination. 99.5 % of the participants responded the questionnaire survey. In the second examination, a total of 223 applicants participated. The examination consisted of 50 multiple-choice questions with cut-off score of 70 per cent score.176 & 194 CTPs passed the first & second examinations respectively. CONCLUSION: This paper that described the results of the two certification tests and questionnaire surveys might be helpful in establishment and activation of the certification program in the future. Quality improvement of CTPs and international competitiveness of clinical trial in Korea can be anticipated by the certification program.