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Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects

The purpose of this study was to perform population pharmacokinetic (PPK) analysis of tiropramide in healthy Korean subjects, as well as to investigate the possible effects of various covariates on pharmacokinetic (PK) parameters of tiropramide. Although tiropramide is commonly used in digestive sys...

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Autores principales: Jeong, Seung-Hyun, Jang, Ji-Hun, Cho, Hea-Young, Lee, Yong-Bok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238185/
https://www.ncbi.nlm.nih.gov/pubmed/32325672
http://dx.doi.org/10.3390/pharmaceutics12040374
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author Jeong, Seung-Hyun
Jang, Ji-Hun
Cho, Hea-Young
Lee, Yong-Bok
author_facet Jeong, Seung-Hyun
Jang, Ji-Hun
Cho, Hea-Young
Lee, Yong-Bok
author_sort Jeong, Seung-Hyun
collection PubMed
description The purpose of this study was to perform population pharmacokinetic (PPK) analysis of tiropramide in healthy Korean subjects, as well as to investigate the possible effects of various covariates on pharmacokinetic (PK) parameters of tiropramide. Although tiropramide is commonly used in digestive system-related diseases as an antispasmodic, PPK reporting and factors affecting PKs are not clearly reported. Thus, this study for healthy subjects is very significant because it could find new covariates in patients that had not been reported before or predict PPK for patients in the clinic by establishing PPK in healthy adults. By using Phoenix NLME, PK, demographic, and genetic data (collected to explain PK diversity of tiropramide in population) analyses were performed. As a basic model, a one-compartment with first-order absorption and lag-time was established and extended to include covariates that influenced the inter-subject variability. The total protein significantly influenced the distribution volume and systemic clearance of tiropramide, but genetic factors such as ABCB1 (1236C>T, 2677G>T/A, and 3435C>T), CYP2D6 (*1 and *10), OCT2 (808G>T), and PEPT1 (1287G>C) genes did not show any significant association with PK parameters of tiropramide. The final PPK model of tiropramide was validated, and suggested that some of the PK diversity in the population could be explained. Herein, we first describe the establishment of the PPK model of tiropramide for healthy Korean subjects, which may be useful as a dosing algorithm for the diseased population.
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spelling pubmed-72381852020-05-28 Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects Jeong, Seung-Hyun Jang, Ji-Hun Cho, Hea-Young Lee, Yong-Bok Pharmaceutics Article The purpose of this study was to perform population pharmacokinetic (PPK) analysis of tiropramide in healthy Korean subjects, as well as to investigate the possible effects of various covariates on pharmacokinetic (PK) parameters of tiropramide. Although tiropramide is commonly used in digestive system-related diseases as an antispasmodic, PPK reporting and factors affecting PKs are not clearly reported. Thus, this study for healthy subjects is very significant because it could find new covariates in patients that had not been reported before or predict PPK for patients in the clinic by establishing PPK in healthy adults. By using Phoenix NLME, PK, demographic, and genetic data (collected to explain PK diversity of tiropramide in population) analyses were performed. As a basic model, a one-compartment with first-order absorption and lag-time was established and extended to include covariates that influenced the inter-subject variability. The total protein significantly influenced the distribution volume and systemic clearance of tiropramide, but genetic factors such as ABCB1 (1236C>T, 2677G>T/A, and 3435C>T), CYP2D6 (*1 and *10), OCT2 (808G>T), and PEPT1 (1287G>C) genes did not show any significant association with PK parameters of tiropramide. The final PPK model of tiropramide was validated, and suggested that some of the PK diversity in the population could be explained. Herein, we first describe the establishment of the PPK model of tiropramide for healthy Korean subjects, which may be useful as a dosing algorithm for the diseased population. MDPI 2020-04-18 /pmc/articles/PMC7238185/ /pubmed/32325672 http://dx.doi.org/10.3390/pharmaceutics12040374 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jeong, Seung-Hyun
Jang, Ji-Hun
Cho, Hea-Young
Lee, Yong-Bok
Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects
title Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects
title_full Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects
title_fullStr Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects
title_full_unstemmed Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects
title_short Population Pharmacokinetic Analysis of Tiropramide in Healthy Korean Subjects
title_sort population pharmacokinetic analysis of tiropramide in healthy korean subjects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238185/
https://www.ncbi.nlm.nih.gov/pubmed/32325672
http://dx.doi.org/10.3390/pharmaceutics12040374
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