Imeglimin Does Not Induce Clinically Relevant Pharmacokinetic Interactions When Combined with Either Metformin or Sitagliptin in Healthy Subjects.
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
pubmed:
10
4
2020
medline:
22
9
2021
entrez:
10
4
2020
Statut:
ppublish
Résumé
Imeglimin (IMEG) is the first in a novel class of oral glucose-lowering agents with a unique mechanism of action targeting mitochondrial bioenergetics. We assessed whether repeated co-administration of IMEG and either metformin (MET) or sitagliptin (SITA) would influence the pharmacokinetics of either MET or SITA in healthy Caucasian men. Healthy Caucasian men received either MET 850 mg twice daily with placebo (n = 16) or SITA 100 mg once daily with placebo (n = 16) on days 1-6, followed by MET 850 mg twice daily with IMEG 1500 mg twice daily or SITA 100 mg once daily with IMEG 1500 mg twice daily on days 7-12. Pharmacokinetic parameters were determined from blood and urine; levels of all compounds were evaluated using liquid chromatography with tandem mass spectrometry. Systemic exposure (AUC Co-administration of IMEG with MET or SITA did not result in clinically relevant changes in systemic exposure to MET or SITA, although minor reductions in exposure (AUC EudraCT2009-014520-40 (MET-IMEG DDI) and EudraCT2010-022926-34 (SITA-IMEG DDI).
Sections du résumé
BACKGROUND AND OBJECTIVES
Imeglimin (IMEG) is the first in a novel class of oral glucose-lowering agents with a unique mechanism of action targeting mitochondrial bioenergetics. We assessed whether repeated co-administration of IMEG and either metformin (MET) or sitagliptin (SITA) would influence the pharmacokinetics of either MET or SITA in healthy Caucasian men.
METHODS
Healthy Caucasian men received either MET 850 mg twice daily with placebo (n = 16) or SITA 100 mg once daily with placebo (n = 16) on days 1-6, followed by MET 850 mg twice daily with IMEG 1500 mg twice daily or SITA 100 mg once daily with IMEG 1500 mg twice daily on days 7-12. Pharmacokinetic parameters were determined from blood and urine; levels of all compounds were evaluated using liquid chromatography with tandem mass spectrometry.
RESULTS
Systemic exposure (AUC
CONCLUSIONS
Co-administration of IMEG with MET or SITA did not result in clinically relevant changes in systemic exposure to MET or SITA, although minor reductions in exposure (AUC
CLINICAL TRIAL REGISTRATION
EudraCT2009-014520-40 (MET-IMEG DDI) and EudraCT2010-022926-34 (SITA-IMEG DDI).
Identifiants
pubmed: 32270440
doi: 10.1007/s40262-020-00886-y
pii: 10.1007/s40262-020-00886-y
doi:
Substances chimiques
Hypoglycemic Agents
0
Triazines
0
Metformin
9100L32L2N
Sitagliptin Phosphate
TS63EW8X6F
imeglimin
UU226QGU97
Banques de données
EudraCT
['EudraCT2009-014520-40', 'EudraCT2010-022926-34']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1261-1271Références
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