Evaluation of the Pharmacokinetic Interaction Between Lobeglitazone and Dapagliflozin at Steady State

Kyungho Jang; Ji-Young Jeon; Seol Ju Moon; Min-Gul Kim

doi:10.1016/j.clinthera.2020.01.003

Evaluation of the Pharmacokinetic Interaction Between Lobeglitazone and Dapagliflozin at Steady State

Clin Ther. 2020 Feb;42(2):295-304. doi: 10.1016/j.clinthera.2020.01.003. Epub 2020 Jan 25.

Authors

Kyungho Jang¹, Ji-Young Jeon², Seol Ju Moon³, Min-Gul Kim⁴

Affiliations

¹ Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, South Korea; Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, South Korea. Electronic address: khjang@jbcp.kr.
² Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, South Korea; Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, South Korea. Electronic address: jyjeon@jbcp.kr.
³ Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, South Korea; Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, South Korea. Electronic address: sjmoon@jbcp.kr.
⁴ Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, South Korea; Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, South Korea; Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, South Korea. Electronic address: mgkim@jbnu.ac.kr.

PMID: 31992459
DOI: 10.1016/j.clinthera.2020.01.003

Abstract

Purpose: Coadministration of lobeglitazone and dapagliflozin is expected to result in a blood glucose-lowering effect, followed by a gradual increase, in clinical usage; however, combining drugs could cause negative interactions. This study aimed to evaluate the effect of the coadministration of lobeglitazone and dapagliflozin on their individual pharmacokinetic properties at steady state in healthy male volunteers in the fasted state.

Methods: This study consisted of 2 parts, each of which was a randomized, open-labeled, multiple-dose, 2-way crossover study in 20 healthy male volunteers in each part. Blood samples were taken periodically over a 48-h period after dosing to derive total plasma lobeglitazone and dapagliflozin pharmacokinetic properties; safety profile was evaluated throughout the study.

Findings: When the pharmacokinetic properties of dapagliflozin were evaluated following its administration alone and in combination with lobeglitazone, point estimate and 90% CI of the geometric mean ratio of dapagliflozin AUC_τ were entirely within the conventional bioequivalence range of 80%-125%. However, although it was not clinically meaningful, its C_ss,max was ~8% lower in subjects receiving multiple doses of dapagliflozin and lobeglitazone than that in those administered dapagliflozin alone. The pharmacokinetic properties of lobeglitazone were evaluated following its administration alone and in combination with dapagliflozin. The geometric mean ratios and 90% CIs of the lobeglitazone C_ss,max and AUC_τ were within the conventional bioequivalence range of 80%-125%.

Implications: Coadministration of lobeglitazone and dapagliflozin had no apparent clinically relevant effects on the pharmacokinetic properties of either drug. Based on these findings, it is anticipated that lobeglitazone and dapagliflozin can be coadministered without dose adjustment. ClinicalTrials.gov identifier: NCT03616392.

Keywords: Drug-drug interaction; Lobeglitazone; Pharmacokinetics; Type 2 diabetes; dapagliflozin.

Publication types

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

MeSH terms

Adult
Benzhydryl Compounds / pharmacokinetics*
Cross-Over Studies
Drug Interactions
Fasting
Glucosides / pharmacokinetics*
Healthy Volunteers
Humans
Hypoglycemic Agents / pharmacokinetics*
Male
Pyrimidines / pharmacokinetics*
Therapeutic Equivalency
Thiazolidinediones / pharmacokinetics*
Young Adult

Substances

Benzhydryl Compounds
Glucosides
Hypoglycemic Agents
Pyrimidines
Thiazolidinediones
dapagliflozin
lobeglitazone

Associated data

ClinicalTrials.gov/NCT03616392