Drug Design, Development and Therapy (Sep 2019)
Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients
Abstract
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 workCorrespondence: Young-Ran YoonDepartment of Molecular Medicine, School of Medicine, Kyungpook National University, 130 Dongduk-Ro, Jung-gu, Daegu 41944, Republic of KoreaTel +82 53 420 4950Fax +82 53 426 4944Email [email protected] Gwang KimDepartment 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 KoreaTel +82 53 200 6522Fax +82 53 420 5218Email [email protected]: 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
