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Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans

Dapagliflozin, a selective sodium–glucose co-transporter-2 inhibitor, and linagliptin, a competitive, reversible dipeptidyl peptidase-4 inhibitor, are commonly prescribed antidiabetic medications in general clinics. Since there are several merits to combining them in a fixed-dose combination product...

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Autores principales: Park, Jin-Woo, Kim, Jong-Min, Noh, Ji Hyeon, Kim, Kyoung-Ah, Chung, Hyewon, Kim, EunJi, Kang, Minja, Park, Ji-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952231/
https://www.ncbi.nlm.nih.gov/pubmed/35335967
http://dx.doi.org/10.3390/pharmaceutics14030591
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author Park, Jin-Woo
Kim, Jong-Min
Noh, Ji Hyeon
Kim, Kyoung-Ah
Chung, Hyewon
Kim, EunJi
Kang, Minja
Park, Ji-Young
author_facet Park, Jin-Woo
Kim, Jong-Min
Noh, Ji Hyeon
Kim, Kyoung-Ah
Chung, Hyewon
Kim, EunJi
Kang, Minja
Park, Ji-Young
author_sort Park, Jin-Woo
collection PubMed
description Dapagliflozin, a selective sodium–glucose co-transporter-2 inhibitor, and linagliptin, a competitive, reversible dipeptidyl peptidase-4 inhibitor, are commonly prescribed antidiabetic medications in general clinics. Since there are several merits to combining them in a fixed-dose combination product, this study investigated the pharmacokinetic equivalence between the individual component (IC) and fixed-combination drug product (FCDP) forms of dapagliflozin and linagliptin. A randomized, open-label, single-dose crossover study was conducted. All participants (n = 48) were randomly allocated to group A (period 1: ICs, period 2: FCDP) or group B (period 1: FCDP, period 2: ICs), and each group received either a single dose of IN-C009 (FCDP) or single doses of both dapagliflozin and linagliptin. There was no statistically significant difference found between the pharmacokinetic variables of FCDP and IC. The values of estimated geometric mean ratios and the 90% confidence interval for both maximum concentration and area under the plasma drug concentration–time curve were within the range of 0.8–1.25 for both dapagliflozin and linagliptin. The results of the clinical study demonstrated comparable pharmacokinetic characteristics between IC and FCDP forms of dapagliflozin and linagliptin. The combined use of dapagliflozin and linagliptin was safe and tolerable in both formulations.
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spelling pubmed-89522312022-03-26 Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans Park, Jin-Woo Kim, Jong-Min Noh, Ji Hyeon Kim, Kyoung-Ah Chung, Hyewon Kim, EunJi Kang, Minja Park, Ji-Young Pharmaceutics Article Dapagliflozin, a selective sodium–glucose co-transporter-2 inhibitor, and linagliptin, a competitive, reversible dipeptidyl peptidase-4 inhibitor, are commonly prescribed antidiabetic medications in general clinics. Since there are several merits to combining them in a fixed-dose combination product, this study investigated the pharmacokinetic equivalence between the individual component (IC) and fixed-combination drug product (FCDP) forms of dapagliflozin and linagliptin. A randomized, open-label, single-dose crossover study was conducted. All participants (n = 48) were randomly allocated to group A (period 1: ICs, period 2: FCDP) or group B (period 1: FCDP, period 2: ICs), and each group received either a single dose of IN-C009 (FCDP) or single doses of both dapagliflozin and linagliptin. There was no statistically significant difference found between the pharmacokinetic variables of FCDP and IC. The values of estimated geometric mean ratios and the 90% confidence interval for both maximum concentration and area under the plasma drug concentration–time curve were within the range of 0.8–1.25 for both dapagliflozin and linagliptin. The results of the clinical study demonstrated comparable pharmacokinetic characteristics between IC and FCDP forms of dapagliflozin and linagliptin. The combined use of dapagliflozin and linagliptin was safe and tolerable in both formulations. MDPI 2022-03-08 /pmc/articles/PMC8952231/ /pubmed/35335967 http://dx.doi.org/10.3390/pharmaceutics14030591 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Jin-Woo
Kim, Jong-Min
Noh, Ji Hyeon
Kim, Kyoung-Ah
Chung, Hyewon
Kim, EunJi
Kang, Minja
Park, Ji-Young
Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans
title Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans
title_full Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans
title_fullStr Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans
title_full_unstemmed Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans
title_short Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans
title_sort pharmacokinetics of a fixed-dose combination product of dapagliflozin and linagliptin and its comparison with co-administration of individual tablets in healthy humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952231/
https://www.ncbi.nlm.nih.gov/pubmed/35335967
http://dx.doi.org/10.3390/pharmaceutics14030591
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