Pharmacokinetic evaluation of novel oral fluorouraci 3ntitumor drug S-1 in Chinese cancer patients

• Published in: 中国药理学报：英文版 2013 (4), p.570-580
• Main Author: Zhi-xiang ZHUANG Hong ZHU Ji WANG Min-gao ZHU Hui WANG Wang-yang PU Hua-hui BIAN Lei CHEN Hong ZHANG
• Format: Article
• Language: English
• Subjects: LC-MS; S-1; 中国; 口服; 生物等效性; 癌症患者; 药代动力学; 评价
• ISSN: 1671-4083; 1745-7254

Aim： S-1 is an oral anticancer fluoropyrimidine formulation consisting of tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate The aim of this study was to evaluate the pharmacokinetics and bioequivalence of a newly developed generic formulation of S-1 in Chi- nese cancer patients in comparison with the branded reference formulation of S-I. Methods： A single-dose, randomized-sequence, open-label, two-way self-crossover study was conducted in 30 Chinese cancer patients. The subjects alternatively received the two formulations （40 mg/m2, po） with a 7-d interval. Plasma concentrations of FT, CDHP, Oxo, and 5-Fu were determined using LC-MS/MS. Pharmacokinetic parameters, including （Cmax, Tmax, t1/2, AUC0-t, and AUC0-∞ were determi- ned using non-compartmental models with DAS2.0 software. Bioequivalence of the two formulations were to be evaluated according to 90% Cls for the log-transformed ratios of AUC and Cmax of S-1. Adverse events were evaluated through monitoring the symptom, phy- sical and laboratory examinations, ECGs and subject interviews. Results： The mean values of Cmax, AUC0-t, and AUC0-∞ of FT, 5-Fu, CDHP, and Oxo for the two formulations had no significant differences The 90% Cls for natural log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were within the predetermined bioequivalence acceptance limits. A total of 11 mild adverse events, including fatigue, nausea and vomiting, anorexia, diarrhea and myelosuppression, were observed, and no serious and special adverse events were found. Conclusion： The newly developed generic formulation and reference formulation of S-1 have similar pharmacokinetics with one dose （40 mg/m2） in Chinese cancer patients. Both the formulations of S-1 are well tolerated.