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Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients

PURPOSE: S-1 is an oral fluoropyrimidine anticancer drug consisting of the 5-fluorouracil prodrug tegafur combined with gimeracil and oteracil. The purpose of this study was to evaluate the pharmacokinetic (PK), bioequivalence, and safety of a newly developed generic formulation of S-1 compared with...

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Autores principales: Lee, Hae Won, Seong, Sook Jin, Kang, Woo Youl, Ohk, Boram, Gwon, Mi-Ri, Kim, Bo Kyung, Cho, Seungil, Cho, Kyunghee, Sung, Yong Kyung, Yoon, Young-Ran, Kim, Jong Gwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732657/
https://www.ncbi.nlm.nih.gov/pubmed/31564829
http://dx.doi.org/10.2147/DDDT.S219822
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author Lee, Hae Won
Seong, Sook Jin
Kang, Woo Youl
Ohk, Boram
Gwon, Mi-Ri
Kim, Bo Kyung
Cho, Seungil
Cho, Kyunghee
Sung, Yong Kyung
Yoon, Young-Ran
Kim, Jong Gwang
author_facet Lee, Hae Won
Seong, Sook Jin
Kang, Woo Youl
Ohk, Boram
Gwon, Mi-Ri
Kim, Bo Kyung
Cho, Seungil
Cho, Kyunghee
Sung, Yong Kyung
Yoon, Young-Ran
Kim, Jong Gwang
author_sort Lee, Hae Won
collection PubMed
description PURPOSE: S-1 is an oral fluoropyrimidine anticancer drug consisting of the 5-fluorouracil prodrug tegafur combined with gimeracil and oteracil. The purpose of this study was to evaluate the pharmacokinetic (PK), bioequivalence, and safety of a newly developed generic formulation of S-1 compared with the branded reference formulation, in Korean gastric cancer patients. METHODS: This was a single-center, randomized, open-label, single-dose, two-treatment, two-way crossover study. Eligible subjects were randomly assigned in a 1:1 ratio to receive the test formulation or reference formulation, followed by a one-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 hrs (predose), 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hrs after dosing in each period. The plasma concentrations of tegafur, 5-FU, gimeracil, and oteracil were analyzed using a validated liquid chromatography-tandem mass spectrometry method. The PK parameters were calculated using a non-compartmental method. RESULTS: In total, 29 subjects completed the study. All of the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) fell within the predetermined acceptance range. No serious adverse events were reported during the study. CONCLUSION: The new S-1 formulation met the Korean regulatory requirement for bioequivalence. Both S-1 formulations were well tolerated in all subjects. Clinical trial registry: https://cris.nih.go.kr CRIS KCT0003855.
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spelling pubmed-67326572019-09-27 Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients Lee, Hae Won Seong, Sook Jin Kang, Woo Youl Ohk, Boram Gwon, Mi-Ri Kim, Bo Kyung Cho, Seungil Cho, Kyunghee Sung, Yong Kyung Yoon, Young-Ran Kim, Jong Gwang Drug Des Devel Ther Original Research PURPOSE: S-1 is an oral fluoropyrimidine anticancer drug consisting of the 5-fluorouracil prodrug tegafur combined with gimeracil and oteracil. The purpose of this study was to evaluate the pharmacokinetic (PK), bioequivalence, and safety of a newly developed generic formulation of S-1 compared with the branded reference formulation, in Korean gastric cancer patients. METHODS: This was a single-center, randomized, open-label, single-dose, two-treatment, two-way crossover study. Eligible subjects were randomly assigned in a 1:1 ratio to receive the test formulation or reference formulation, followed by a one-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 hrs (predose), 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hrs after dosing in each period. The plasma concentrations of tegafur, 5-FU, gimeracil, and oteracil were analyzed using a validated liquid chromatography-tandem mass spectrometry method. The PK parameters were calculated using a non-compartmental method. RESULTS: In total, 29 subjects completed the study. All of the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) fell within the predetermined acceptance range. No serious adverse events were reported during the study. CONCLUSION: The new S-1 formulation met the Korean regulatory requirement for bioequivalence. Both S-1 formulations were well tolerated in all subjects. Clinical trial registry: https://cris.nih.go.kr CRIS KCT0003855. Dove 2019-09-03 /pmc/articles/PMC6732657/ /pubmed/31564829 http://dx.doi.org/10.2147/DDDT.S219822 Text en © 2019 Lee et al. http://creativecommons.org/licenses/by-nc/3.0/ 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Lee, Hae Won
Seong, Sook Jin
Kang, Woo Youl
Ohk, Boram
Gwon, Mi-Ri
Kim, Bo Kyung
Cho, Seungil
Cho, Kyunghee
Sung, Yong Kyung
Yoon, Young-Ran
Kim, Jong Gwang
Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
title Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
title_full Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
title_fullStr Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
title_full_unstemmed Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
title_short Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
title_sort pharmacokinetic and bioequivalence study between two formulations of s-1 in korean gastric cancer patients
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732657/
https://www.ncbi.nlm.nih.gov/pubmed/31564829
http://dx.doi.org/10.2147/DDDT.S219822
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