![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
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.
Acknowledgment
This study was sponsored by Myungmoon Pharm. Co., Ltd., Seoul, Republic of Korea, and was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2750, HI15C0001), as well as by the Industrial Core Technology Development Program (10051129, Development of the system for ADME assessment using radiolabeled compounds), funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).
Data sharing statement
We, the authors, intend to share individual de-identified participant data. However, there must be a limit on our data sharing, because this study was sponsored by a pharmaceutical company.
Disclosure
At the time of the study, KC was employed by Biocore Co. Ltd. and YKS was employed by Myungmoon Pharm. Co., Ltd. The authors report no other conflicts of interest in this work.