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Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen

OBJECTIVE: Prostaglandin E(2) (PGE(2)) synthesis is modulated by COX2. Changes in PGE(2) could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of...

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Autores principales: Shin, Dongseong, Lee, Sook Joung, Ha, Yu-Mi, Choi, Young-Sim, Kim, Jae-Won, Park, Se-Rin, Park, Min Kyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221548/
https://www.ncbi.nlm.nih.gov/pubmed/28115830
http://dx.doi.org/10.2147/DDDT.S121633
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author Shin, Dongseong
Lee, Sook Joung
Ha, Yu-Mi
Choi, Young-Sim
Kim, Jae-Won
Park, Se-Rin
Park, Min Kyu
author_facet Shin, Dongseong
Lee, Sook Joung
Ha, Yu-Mi
Choi, Young-Sim
Kim, Jae-Won
Park, Se-Rin
Park, Min Kyu
author_sort Shin, Dongseong
collection PubMed
description OBJECTIVE: Prostaglandin E(2) (PGE(2)) synthesis is modulated by COX2. Changes in PGE(2) could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects. MATERIALS AND METHODS: A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE(2) inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE(2) was applied to the pharmacodynamic evaluation. RESULTS: After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration–time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE(2) WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%. CONCLUSION: Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme.
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spelling pubmed-52215482017-01-23 Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen Shin, Dongseong Lee, Sook Joung Ha, Yu-Mi Choi, Young-Sim Kim, Jae-Won Park, Se-Rin Park, Min Kyu Drug Des Devel Ther Original Research OBJECTIVE: Prostaglandin E(2) (PGE(2)) synthesis is modulated by COX2. Changes in PGE(2) could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects. MATERIALS AND METHODS: A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE(2) inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE(2) was applied to the pharmacodynamic evaluation. RESULTS: After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration–time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE(2) WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%. CONCLUSION: Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme. Dove Medical Press 2017-01-04 /pmc/articles/PMC5221548/ /pubmed/28115830 http://dx.doi.org/10.2147/DDDT.S121633 Text en © 2017 Shin et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Shin, Dongseong
Lee, Sook Joung
Ha, Yu-Mi
Choi, Young-Sim
Kim, Jae-Won
Park, Se-Rin
Park, Min Kyu
Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen
title Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen
title_full Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen
title_fullStr Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen
title_full_unstemmed Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen
title_short Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen
title_sort pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221548/
https://www.ncbi.nlm.nih.gov/pubmed/28115830
http://dx.doi.org/10.2147/DDDT.S121633
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