Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
Received 17 June 2019
Accepted for publication 3 August 2019
Published 3 September 2019 Volume 2019:13 Pages 3127—3136
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
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
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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