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Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: A Randomized, Open-label Study in Healthy Mexican Volunteers.
Clin Ther. 2018 10; 40(10):1729-1740.CT

Abstract

PURPOSE

The aim of this study was to assess the pharmacokinetic interactions between a newly developed dipeptidyl peptidase (DPP)-4 inhibitor, gemigliptin, and metformin in healthy Mexican male volunteers, and the differences in the pharmacokinetic profile of gemigliptin between Korean and Mexican healthy volunteers.

METHODS

This was a multiple-dose, randomized, open-label, 3-way, 3-period crossover study. Subjects were randomized to 1 of 3 treatment sequences and received gemigliptin 50mg once a day, metformin1000mg BID, or both drugs during a 7-day treatment period, and underwent sampling for pharmacokinetic analysis and tolerability assessments. Point estimates and 90% CIs of Cmax,ss and AUCτ,ss least squares mean (LSM) ratios of the concurrent administration of gemigliptin + metformin to the administration of monotherapy with either drug were obtained, and the pharmacokinetic profile of gemigliptin observed was compared with that in healthy Korean volunteers studied during the initial development of gemigliptin.

FINDINGS

The coadministration of gemigliptin + metformin did not affect the pharmacokinetic characteristics of gemigliptin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.98 [0.87-1.10] and 0.94 [0.91-0.98], respectively) or metformin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.97 [0.88-1.08] and 1.02 [0.93-1.12], respectively) when administered as monotherapy and was well tolerated. In contrast with Korean healthy volunteers, Mexican subjects showed a modestly higher gemigliptin exposure (LSM ratio [90% CI] for AUCτ,ss: 1.22 [1.14-1.31]).

IMPLICATIONS

The results of this study support, in ethnically different populations, the absence of drug-drug interactions between gemigliptin and metformin previously shown in Korean healthy volunteers. Considering the flat effect-concentration curve and wide therapeutic range of gemigliptin, the pharmacokinetic profile of gemigliptin observed in healthy Mexican and Korean subjects suggests that gemigliptin use in Mexican patients may be associated with outcomes, in terms of efficacy and tolerability, similar to those observed in the Korean population. ClinicalTrials.gov identifier: NCT03310749.

Authors+Show Affiliations

Específicos Stendhal SA de CV, Mexico City, Mexico. Electronic address: Ignacio.conde@stendhalpharma.com.Clinical Pharmacology Unit, Faculty of Medicine, Autonomous National University of Mexico, Mexico City, Mexico.Clinical Pharmacology Unit, Faculty of Medicine, Autonomous National University of Mexico, Mexico City, Mexico.Clinical Pharmacology Unit, Faculty of Medicine, Autonomous National University of Mexico, Mexico City, Mexico.Drug Metabolism and Pharmacokinetics, LG Chem, Ltd, Life Sciences R&D, Diabetes Center, Seoul, Republic of Korea.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30249366

Citation

Conde-Carmona, Ignacio, et al. "Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: a Randomized, Open-label Study in Healthy Mexican Volunteers." Clinical Therapeutics, vol. 40, no. 10, 2018, pp. 1729-1740.
Conde-Carmona I, García-Medina S, Jiménez-Vargas JM, et al. Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: A Randomized, Open-label Study in Healthy Mexican Volunteers. Clin Ther. 2018;40(10):1729-1740.
Conde-Carmona, I., García-Medina, S., Jiménez-Vargas, J. M., Martínez-Muñoz, A., & Lee, S. H. (2018). Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: A Randomized, Open-label Study in Healthy Mexican Volunteers. Clinical Therapeutics, 40(10), 1729-1740. https://doi.org/10.1016/j.clinthera.2018.08.015
Conde-Carmona I, et al. Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: a Randomized, Open-label Study in Healthy Mexican Volunteers. Clin Ther. 2018;40(10):1729-1740. PubMed PMID: 30249366.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: A Randomized, Open-label Study in Healthy Mexican Volunteers. AU - Conde-Carmona,Ignacio, AU - García-Medina,Sandra, AU - Jiménez-Vargas,Juan M, AU - Martínez-Muñoz,Alberto, AU - Lee,Sung-Hack, Y1 - 2018/09/22/ PY - 2018/04/02/received PY - 2018/08/07/revised PY - 2018/08/22/accepted PY - 2018/9/27/pubmed PY - 2019/9/19/medline PY - 2018/9/26/entrez KW - diabetes KW - dipeptidy-peptidase-4 inhibitor KW - drug–drug interactions KW - gemigliptin KW - type 2 drug therapy SP - 1729 EP - 1740 JF - Clinical therapeutics JO - Clin Ther VL - 40 IS - 10 N2 - PURPOSE: The aim of this study was to assess the pharmacokinetic interactions between a newly developed dipeptidyl peptidase (DPP)-4 inhibitor, gemigliptin, and metformin in healthy Mexican male volunteers, and the differences in the pharmacokinetic profile of gemigliptin between Korean and Mexican healthy volunteers. METHODS: This was a multiple-dose, randomized, open-label, 3-way, 3-period crossover study. Subjects were randomized to 1 of 3 treatment sequences and received gemigliptin 50mg once a day, metformin1000mg BID, or both drugs during a 7-day treatment period, and underwent sampling for pharmacokinetic analysis and tolerability assessments. Point estimates and 90% CIs of Cmax,ss and AUCτ,ss least squares mean (LSM) ratios of the concurrent administration of gemigliptin + metformin to the administration of monotherapy with either drug were obtained, and the pharmacokinetic profile of gemigliptin observed was compared with that in healthy Korean volunteers studied during the initial development of gemigliptin. FINDINGS: The coadministration of gemigliptin + metformin did not affect the pharmacokinetic characteristics of gemigliptin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.98 [0.87-1.10] and 0.94 [0.91-0.98], respectively) or metformin (LSM ratio [90% CI] for Cmax,ss and AUCτ,ss: 0.97 [0.88-1.08] and 1.02 [0.93-1.12], respectively) when administered as monotherapy and was well tolerated. In contrast with Korean healthy volunteers, Mexican subjects showed a modestly higher gemigliptin exposure (LSM ratio [90% CI] for AUCτ,ss: 1.22 [1.14-1.31]). IMPLICATIONS: The results of this study support, in ethnically different populations, the absence of drug-drug interactions between gemigliptin and metformin previously shown in Korean healthy volunteers. Considering the flat effect-concentration curve and wide therapeutic range of gemigliptin, the pharmacokinetic profile of gemigliptin observed in healthy Mexican and Korean subjects suggests that gemigliptin use in Mexican patients may be associated with outcomes, in terms of efficacy and tolerability, similar to those observed in the Korean population. ClinicalTrials.gov identifier: NCT03310749. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/30249366/Pharmacokinetic_Interactions_Between_Gemigliptin_and_Metformin_and_Potential_Differences_in_the_Pharmacokinetic_Profile_of_Gemigliptin_Between_the_Mexican_and_Korean_Populations:_A_Randomized_Open_label_Study_in_Healthy_Mexican_Volunteers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(18)30378-3 DB - PRIME DP - Unbound Medicine ER -