PMID- 23100167
OWN - NLM
STAT- MEDLINE
DCOM- 20130501
LR  - 20211021
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 32
IP  - 12
DP  - 2012 Dec
TI  - Pharmacokinetics of a fixed-dose combination of mitiglinide and metformin versus 
      concurrent administration of individual formulations in healthy subjects: a 
      randomized, open-label, two-treatment, two-period, two-sequence, single-dose, 
      crossover study.
PG  - 799-804
LID - 10.1007/s40261-012-0012-6 [doi]
AB  - BACKGROUND: In the treatment of diabetes mellitus, combined drugs with different 
      mechanisms of action can be effective when adequate glycaemic control is 
      difficult with monotherapy. A fixed-dose combination (FDC) tablet of mitiglinide 
      and metformin has been developed as a second-line treatment for type 2 diabetes. 
      OBJECTIVES: The objective of this study was to compare the pharmacokinetics and 
      safety of a FDC and a free combination of mitiglinide and metformin in healthy 
      male subjects. METHODS: A randomized, open-label, two-period, two-treatment, 
      single-dose, crossover study was conducted in 24 healthy Korean male subjects. In 
      one period, a FDC tablet of mitiglinide and metformin (10 mg/500 mg) was 
      administered, and in the other period, corresponding doses of individual 
      formulations were administered. RESULTS: Twenty-four subjects were enrolled and 
      19 subjects completed the study. The geometric mean ratios (90 % confidence 
      interval) of the maximum plasma concentration (C(max)) and area under the plasma 
      concentration-time curve from time zero to the time of the last measurable 
      concentration (AUC(last)) were 0.9694 (0.8120, 1.1573) and 0.8951 (0.8440, 
      0.9494) for mitiglinide, and 1.0235 (0.9373, 1.1057) and 1.0542 (0.9697, 1.1460) 
      for metformin, which were within the bioequivalence range. Among the 23 subjects 
      who received study drugs, 15 subjects experienced 34 adverse events (AEs). The 
      most frequently reported AEs were feeling hot and compensatory sweating. There 
      were no serious AEs and no significant differences in the incidence of AEs 
      between the two treatments. CONCLUSION: A FDC tablet of mitiglinide and metformin 
      was generally well tolerated in healthy male subjects. Administration of a FDC 
      tablet and concomitant administration of individual formulations did not show 
      significantly different pharmacokinetic profiles.
FAU - Jung, Jin Ah
AU  - Jung JA
AD  - Department of Clinical Pharmacology and Therapeutic, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Gangnam-Gu, Seoul, Korea.
FAU - Kim, Jung-Ryul
AU  - Kim JR
FAU - Kim, Suk-Ran
AU  - Kim SR
FAU - Kim, Tae-Eun
AU  - Kim TE
FAU - Lee, Soo-Youn
AU  - Lee SY
FAU - Ko, Jae-Wook
AU  - Ko JW
FAU - Huh, Wooseong
AU  - Huh W
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Drug Combinations)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Isoindoles)
RN  - 0 (Tablets)
RN  - 9100L32L2N (Metformin)
RN  - D86I0XLB13 (mitiglinide)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Drug Combinations
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - Isoindoles/administration & dosage/adverse effects/*pharmacokinetics
MH  - Male
MH  - Metformin/administration & dosage/adverse effects/*pharmacokinetics
MH  - Republic of Korea
MH  - Tablets
MH  - Young Adult
EDAT- 2012/10/27 06:00
MHDA- 2013/05/02 06:00
CRDT- 2012/10/27 06:00
PHST- 2012/10/27 06:00 [entrez]
PHST- 2012/10/27 06:00 [pubmed]
PHST- 2013/05/02 06:00 [medline]
AID - 10.1007/s40261-012-0012-6 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2012 Dec;32(12):799-804. doi: 10.1007/s40261-012-0012-6.