title: Pharmacokinetic evaluation of novel oral fluorouracil antitumor drug S-1 in Chinese cancer patients.
abstract: OBJECTIVE
  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 Chinese cancer patients in comparison with the branded reference formulation of S-1.
  
  
  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/m(2), 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 determined using non-compartmental models with DAS2.0 software. Bioequivalence of the two formulations were to be evaluated according to 90% CIs for the log-transformed ratios of AUC and Cmax of S-1. Adverse events were evaluated through monitoring the symptom, physical 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% CIs 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.
  
  
  CONCLUSIONS
  The newly developed generic formulation and reference formulation of S-1 have similar pharmacokinetics with one dose (40 mg/m(2)) in Chinese cancer patients. Both the formulations of S-1 are well tolerated.
authors: Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors: Zhi-xiang
authors: ZX
authors: Zhuang
authors: Hong
authors: H
authors: Zhu
authors: Ji
authors: J
authors: Wang
authors: Min-gao
authors: MG
authors: Zhu
authors: Hui
authors: H
authors: Wang
authors: Wang-yang
authors: WY
authors: Pu
authors: Hua-hui
authors: HH
authors: Bian
authors: Lei
authors: L
authors: Chen
authors: Hong
authors: H
authors: Zhang
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics*; D044466:Asian People; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: C417063:5-chlorodihydroxypyridine; D000970:Antineoplastic Agents; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; C489337:potassium oxonate; D010094:Oxonic Acid; D005472:Fluorouracil
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