Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers.
OBJECTIVE
For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets.


METHODS
This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg × 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from predose to 48 hours after dosing. Tolerability assessments were performed throughout the study.


RESULTS
Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the Cmax and AUClast were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the Cmax and AUClast were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged tmax for metformin was observed. These results are similar to the effects of food on each component.


CONCLUSIONS
The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.
Hee Youn
HY
Choi
Yook-Hwan
YH
Noh
Yo Han
YH
Kim
Mi Jo
MJ
Kim
Shi Hyang
SH
Lee
Jeong-Ae
JA
Kim
Bogyeong
B
Kim
Hyeong-Seok
HS
Lim
Kyun-Seop
KS
Bae
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005215:Fasting / Q000097:blood; D018565:Food-Drug Interactions; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D010881:Piperidones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019518:Postprandial Period; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D056910:Republic of Korea; D012737:Sex Factors; D013607:Tablets; D055815:Young Adult
D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007004:Hypoglycemic Agents; C534891:LC15-0444; D010881:Piperidones; D011743:Pyrimidines; D013607:Tablets; D008687:Metformin