Investigation of bioequivalence of a new fixed-dose combination of acarbose and metformin with the corresponding loose combination as well as the drug-drug interaction potential between both drugs in healthy adult male subjects.
What is known and objective Both metformin and acarbose are recommended monotherapy and add-on therapy in type 2 diabetes mellitus ( T2 DM). A fixed-dose combination ( FDC) of acarbose and metformin has been developed to reduce pill burden and potentially improve compliance. The current study invest...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 39; no. 4; pp. 424 - 432 |
|---|---|
| Autores principales: | , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Aug2014
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103969952&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103969952 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Aug2014 vid: 39 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 103969952 96937042 10.1111/jcpt.12166 NLM24806030 103969952 ppf: 424 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Investigation of bioequivalence of a new fixed-dose combination of acarbose and metformin with the corresponding loose combination as well as the drug-drug interaction potential between both drugs in healthy adult male subjects. aug: au: Kim, S. Jang, I.-J. Shin, D. Shin, D. S. Yoon, S. Lim, K. S. Yu, K.-S. Li, J. Zhang, H. Liu, Y. Brendel, E. Blode, H. Wang, Y. affil: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital sug: subj: Diabetes Mellitus, Type 2 Drug Therapy Acarbose Pharmacokinetics Metformin Pharmacokinetics Acarbose Pharmacodynamics Metformin Pharmacodynamics Drug Combinations Biological Availability Drug Therapy, Combination Human Drug Tolerance Patient Safety Drug Interactions Crossover Design Male Koreans Acarbose Administration and Dosage Metformin Administration and Dosage Descriptive Statistics Confidence Intervals Adverse Drug Event Chromatography, High Pressure Liquid Data Analysis Software Blood Chemical Analysis Analysis of Variance Blood Glucose Funding Source Adolescence Young Adult Adult Middle Age Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Male ab: What is known and objective Both metformin and acarbose are recommended monotherapy and add-on therapy in type 2 diabetes mellitus ( T2 DM). A fixed-dose combination ( FDC) of acarbose and metformin has been developed to reduce pill burden and potentially improve compliance. The current study investigated the bioequivalence of the acarbose/metformin FDC compared with the individual agents administered simultaneously (loose combination). Secondary endpoints were the safety and tolerability of the FDC and the potential for drug-drug interactions between acarbose and metformin. Methods A single-centre, randomized, open-label, four-period crossover study was conducted in healthy male Korean subjects aged 18-45 years. Following one-period balanced Williams design, participants were randomized to receive four single oral treatments on different study days separated by ≥7 days' washout. Treatments were as follows: (i) acarbose/metformin 50/500 mg FDC (test); (ii) acarbose 50 mg and metformin 500 mg as loose combination (reference); (iii) acarbose 50 mg; and (iv) metformin 500 mg. Serial blood samples were taken for glucose and insulin levels for 4 h after a sucrose load on the day before and day of study drug administration. Additionally, serial blood samples were taken for analysis of metformin levels for 24 h after each drug containing metformin. The area under the curve for 4 h post-test ( AUC0-4 h) and the maximal serum concentration ( Cmax) of plasma glucose and serum insulin were primary pharmacodynamic ( PD) parameters, and Cmax, AUC0-last and AUC for metformin levels were primary pharmacokinetic ( PK) parameters. The bioequivalence of the FDC to the loose combination was considered established if the 90% confidence intervals ( CIs) of the baseline-adjusted PD parameter ratios (test vs. reference) for plasma glucose and the PK parameter ratios for metformin fell completely within current acceptance limits (0·8-1·25). Results and discussion Thirty-three of 40 randomized subjects completed the study; five withdrew consent and two discontinued because of adverse events ( AEs). The 24-h plasma concentration-time curves of metformin and the 4-h plasma glucose-time curves after acarbose/metformin FDC (test) and acarbose + metformin loose combination (reference) were almost superimposable. The geometric least squares ( LS) mean of the Ratio AUC and pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|