title: Two dosages of oral fluoropyrimidine S-1 of 35 and 40 mg/m2 bid: comparison of the pharmacokinetic profiles in Korean patients with advanced gastric cancer.
abstract: OBJECTIVE
  In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m(2) bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer.
  
  
  METHODS
  Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m(2), ranging from 70 to 88 mg/m(2).
  
  
  RESULTS
  Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C(max) and AUC(0-48 h) values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity.
  
  
  CONCLUSIONS
  We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.
authors.affiliation: Cancer Metastasis Research Center, Department of Medical Oncology, Yonsei University College of Medicine, 250 Seongsanno (134, Shinchon-Dong), Seodaemun-Gu, Seoul 120-752, Korea.
authors.forename: Hei-Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid