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

Authors Lee HW, Seong SJ, Kang WY, Ohk B, Gwon MR, Kim BK, Cho S, Cho K, Sung YK, Yoon YR, Kim JG

Received 17 June 2019

Accepted for publication 3 August 2019

Published 3 September 2019 Volume 2019:13 Pages 3127—3136

DOI https://doi.org/10.2147/DDDT.S219822

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Hae Won Lee*,1,2, Sook Jin Seong*,1,2, Woo Youl Kang1,2, Boram Ohk1,2, Mi-Ri Gwon1,2, Bo Kyung Kim1,2, Seungil Cho1,2, Kyunghee Cho3, Yong Kyung Sung4, Young-Ran Yoon1,2, Jong Gwang Kim5

1Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea; 3Analytical Research Division, Biocore Co. Ltd., Seoul, Republic of Korea; 4Department of R&D, Myungmoon Pharm. Co., Ltd., Seoul, Republic of Korea; 5Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu, Republic of Korea

*These authors contributed equally to this work

Correspondence: Young-Ran Yoon
Department of Molecular Medicine, School of Medicine, Kyungpook National University, 130 Dongduk-Ro, Jung-gu, Daegu 41944, Republic of Korea
Tel +82 53 420 4950
Fax +82 53 426 4944
Email yry@knu.ac.kr

Jong Gwang Kim
Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, 130 Dongduk-Ro, Jung-gu, Daegu 41944, Republic of Korea
Tel +82 53 200 6522
Fax +82 53 420 5218
Email jkk21c@knu.ac.kr

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.

Keywords: S-1, pharmacokinetics, bioequivalence, tegafur, gimeracil, oteracil

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