PMID- 20678687
OWN - NLM
STAT- MEDLINE
DCOM- 20101122
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 32
IP  - 7
DP  - 2010 Jul
TI  - Comparison of the bioavailability and tolerability of fixed-dose combination 
      glimepiride/metformin 2/500-mg tablets versus separate tablets: A single-dose, 
      randomized-sequence, open-label, two-period crossover study in healthy Korean 
      volunteers.
PG  - 1408-18
LID - 10.1016/j.clinthera.2010.07.012 [doi]
AB  - OBJECTIVE: This study compared the bioavailability and tolerability of a 
      fixed-dose combination (FDC) tablet of glimepiride/metformin 2/500 mg and 
      glimepiride 2-mg + metformin 500-mg tablets administered separately in healthy 
      Korean subjects. METHODS: In this single-dose, open-label, 2-period crossover 
      study, healthy Korean volunteers were randomly assigned to receive, in 1 of 2 
      randomized sequences, an FDC tablet of glimepiride/metformin 2/500 mg (test) and 
      glimepiride 2-mg + metformin 500-mg tablets administered separately (reference), 
      with a 1-week washout period between treatments. Plasma concentrations of 
      glimepiride and metformin were measured using LC/MS-MS. Pharmacokinetic 
      parameters were analyzed using noncompartmental methods. Bioequivalence was 
      concluded if the 90% CIs of the geometric mean test/reference ratios (GMRs) of 
      the logarithm-transformed C(max), AUC from 0 to 30 hours (AUC(0-30)), and 
      AUC(0-infinity) values were within the predetermined regulatory range of 80% to 
      125%. Tolerability was assessed using physical examination and laboratory 
      analysis. RESULTS: A total of 32 subjects were enrolled (16 men [mean (SD) age, 
      21.8 (2.7) years (range, 18-26 years); weight, 68.9 (8.3) kg (range, 55.5-85.0 
      kg)]; 16 women [age, 23.5 (4.5) years (range, 20-38 years); weight, 51.7 (3.5) kg 
      (range, 46.8-58.0 kg)]). The GMRs (90% CI) of glimepiride C(max), AUC(0-30), and 
      AUC(0-infinity) were 1.01 (0.91-1.11), 0.98 (0.92-1.03), and 0.97 (0.93-1.04), 
      respectively. For metformin, these values were 0.96 (0.87-1.06), 0.96 
      (0.90-1.03), and 0.96 (0.90-1.03). A total of 49 adverse events (AEs) were 
      reported in 10 subjects (31.3%) with the FDC and in 13 subjects (40.6%) with the 
      separate tablets. The most commonly reported AEs with the test and reference 
      treatments were dizziness (6 [19%] and 7 [22%]) and sweating (4 [13%] and 7 
      [22%]), respectively. The severity of all of the AEs was considered to be mild, 
      and there were no significant differences in the prevalences of AEs between the 2 
      formulations. CONCLUSIONS: In this study in healthy Korean subjects, the 
      requirements for bioequivalence of the glimepiride/metformin 2/500-mg FDC and 
      coadministration of separate tablets of each drug were met. Both formulations 
      were generally well tolerated.
CI  - 2010 Excerpta Medica Inc. All rights reserved.
FAU - Gu, Namyi
AU  - Gu N
AD  - Department of Pharmacology and Clinical Pharmacology, Seoul National University 
      College of Medicine and Hospital, Korea.
FAU - Kim, Bo-Hyung
AU  - Kim BH
FAU - Rhim, HyouYoung
AU  - Rhim H
FAU - Chung, Jae-Yong
AU  - Chung JY
FAU - Kim, Jung-Ryul
AU  - Kim JR
FAU - Shin, Hyun-Suk
AU  - Shin HS
FAU - Yoon, Seo-Hyun
AU  - Yoon SH
FAU - Cho, Joo-Youn
AU  - Cho JY
FAU - Shin, Sang-Goo
AU  - Shin SG
FAU - Jang, In-Jin
AU  - Jang IJ
FAU - Yu, Kyung-Sang
AU  - Yu KS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Drug Combinations)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sulfonylurea Compounds)
RN  - 0 (Tablets)
RN  - 6KY687524K (glimepiride)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Asian People
MH  - Chromatography, Liquid/methods
MH  - Cross-Over Studies
MH  - Drug Combinations
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - Korea
MH  - Male
MH  - Metformin/administration & dosage/adverse effects/*pharmacokinetics
MH  - Sulfonylurea Compounds/administration & dosage/adverse effects/*pharmacokinetics
MH  - Tablets
MH  - Tandem Mass Spectrometry/methods
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2010/08/04 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/08/04 06:00
PHST- 2010/06/15 00:00 [accepted]
PHST- 2010/08/04 06:00 [entrez]
PHST- 2010/08/04 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0149-2918(10)00239-0 [pii]
AID - 10.1016/j.clinthera.2010.07.012 [doi]
PST - ppublish
SO  - Clin Ther. 2010 Jul;32(7):1408-18. doi: 10.1016/j.clinthera.2010.07.012.